Amitriptyline (T3D2480)
| Record Information | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Version | 2.0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Creation Date | 2009-07-03 22:04:59 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Update Date | 2014-12-24 20:25:34 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | T3D2480 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Identification | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Common Name | Amitriptyline | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Small Molecule | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | Amitriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amitriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, amitriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amitriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis (unlabeled use). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Compound Type |
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| Chemical Structure |  | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synonyms |
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| Chemical Formula | C20H23N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Average Molecular Mass | 277.403 g/mol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monoisotopic Mass | 277.183 g/mol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAS Registry Number | 50-48-6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IUPAC Name | dimethyl(3-{tricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Traditional Name | amitriptyline | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SMILES | CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Identifier | InChI=1S/C20H23N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-12H,7,13-15H2,1-2H3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=KRMDCWKBEZIMAB-UHFFFAOYSA-N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Taxonomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | belongs to the class of organic compounds known as dibenzocycloheptenes. Dibenzocycloheptenes are compounds containing a dibenzocycloheptene moiety, which consists of two benzene rings connected by a cycloheptene ring. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic compounds | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Super Class | Benzenoids | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Dibenzocycloheptenes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sub Class | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Direct Parent | Dibenzocycloheptenes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative Parents | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Substituents |
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| Molecular Framework | Aromatic homopolycyclic compounds | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Descriptors |
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| Biological Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status | Detected and Not Quantified | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Origin | Exogenous | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cellular Locations |
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| Biofluid Locations | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tissue Locations | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pathways | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Applications | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological Roles | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Roles | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Physical Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| State | Solid | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Appearance | White, odorless, crystalline compound (4). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Spectra | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Spectra |
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| Toxicity Profile | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Route of Exposure | Oral (1) Rapidly and well absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations occur 2-12 hours following oral or intramuscular administration. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mechanism of Toxicity | Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Metabolism | Amitriptyline is rapidly and well absorbed following oral administration. Exclusively hepatic, with first pass effect. Amitriptyline is demethylated in the liver to its primary active metabolite, nortriptyline. Route of Elimination: Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours. Small amounts are excreted in feces via biliary elimination. Half Life: 10 to 50 hours, with an average of 15 hours | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Toxicity Values | LD50: 350 mg/kg (Oral, Mouse) (1) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lethal Dose | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Uses/Sources | For the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Minimum Risk Level | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Health Effects | Some rare side effects include tinnitus, hypotension, mania, psychosis, heart block, arrhythmias, lip and mouth ulcers, extrapyramidal symptoms, depression, and hepatic toxicity.Amitriptyline exhibits strong anticholinergic activity, cardiovascular effects including orthostatic hypotension, changes in heart rhythm and conduction, and a lowering of the seizure threshold (1, 4). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Symptoms | Symptoms of overdose include abnormally low blood pressure, confusion, convulsions, dilated pupils and other eye problems, disturbed concentration, drowsiness, hallucinations, impaired heart function, rapid or irregular heartbeat, reduced body temperature, stupor, and unresponsiveness or coma. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Treatment | Consider gastric lavage only if within one hour of a potentially fatal overdose. Give 50 grams of charcoal if within one hour of ingestion. Prolonged resuscitation may be successful in case of cardiac arrest. Give sodium bicarbonate in case of arrhythmias. (2) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Normal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abnormal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Links | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DrugBank ID | DB00321 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HMDB ID | HMDB14466 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PubChem Compound ID | 2160 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChEMBL ID | CHEMBL629 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChemSpider ID | 2075 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| KEGG ID | C06824 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UniProt ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| OMIM ID | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChEBI ID | 2666 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BioCyc ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CTD ID | D000639 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Stitch ID | Amitriptyline | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PDB ID | TP0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ACToR ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikipedia Link | Amitriptyline | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| References | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synthesis Reference | Manfred Durr, Benedikt Gajdos, Klaus-Dieter Gneuss, Ekkehard Harhausen, Jurgen Seidel, “Pharmaceutical amitriptylin oxide preparation and process for its manufacture.” U.S. Patent US4567202, issued January 28, 1986. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MSDS | Link | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| General References |
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| Gene Regulation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Up-Regulated Genes |
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| Down-Regulated Genes |
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Targets
- General Function:
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function:
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
- Gene Name:
- KCNH2
- Uniprot ID:
- Q12809
- Molecular Weight:
- 126653.52 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 10 uM | Not Available | BindingDB 50020712 |
References
- Cavalli A, Poluzzi E, De Ponti F, Recanatini M: Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers. J Med Chem. 2002 Aug 29;45(18):3844-53. [12190308 ]
- Keseru GM: Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5. [12873512 ]
- Rajamani R, Tounge BA, Li J, Reynolds CH: A two-state homology model of the hERG K+ channel: application to ligand binding. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1737-41. [15745831 ]
- Tobita M, Nishikawa T, Nagashima R: A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2886-90. [15911273 ]
- Jia L, Sun H: Support vector machines classification of hERG liabilities based on atom types. Bioorg Med Chem. 2008 Jun 1;16(11):6252-60. doi: 10.1016/j.bmc.2008.04.028. Epub 2008 Apr 16. [18448342 ]
- Ermondi G, Visentin S, Caron G: GRIND-based 3D-QSAR and CoMFA to investigate topics dominated by hydrophobic interactions: the case of hERG K+ channel blockers. Eur J Med Chem. 2009 May;44(5):1926-32. doi: 10.1016/j.ejmech.2008.11.009. Epub 2008 Nov 28. [19110341 ]
- General Function:
- Serotonin:sodium symporter activity
- Specific Function:
- Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
- Gene Name:
- SLC6A4
- Uniprot ID:
- P31645
- Molecular Weight:
- 70324.165 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.0028 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.00345 uM | Not Available | BindingDB 50020712 |
References
- Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [14744476 ]
- Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2. [16140280 ]
- Troelsen KB, Nielsen EO, Mirza NR: Chronic treatment with duloxetine is necessary for an anxiolytic-like response in the mouse zero maze: the role of the serotonin transporter. Psychopharmacology (Berl). 2005 Oct;181(4):741-50. Epub 2005 Sep 29. [16032412 ]
- Ushijima K, Sakaguchi H, Sato Y, To H, Koyanagi S, Higuchi S, Ohdo S: Chronopharmacological study of antidepressants in forced swimming test of mice. J Pharmacol Exp Ther. 2005 Nov;315(2):764-70. Epub 2005 Aug 3. [16079297 ]
- Kalia M: Neurobiological basis of depression: an update. Metabolism. 2005 May;54(5 Suppl 1):24-7. [15877309 ]
- Owens MJ, Morgan WN, Plott SJ, Nemeroff CB: Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther. 1997 Dec;283(3):1305-22. [9400006 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
- Gene Name:
- HTR2C
- Uniprot ID:
- P28335
- Molecular Weight:
- 51820.705 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.018 uM | Not Available | BindingDB 50020712 |
References
- Di Matteo V, De Blasi A, Di Giulio C, Esposito E: Role of 5-HT(2C) receptors in the control of central dopamine function. Trends Pharmacol Sci. 2001 May;22(5):229-32. [11339973 ]
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- Chanrion B, Mannoury la Cour C, Gavarini S, Seimandi M, Vincent L, Pujol JF, Bockaert J, Marin P, Millan MJ: Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulation of cell surface expression and signal transduction. Mol Pharmacol. 2008 Mar;73(3):748-57. Epub 2007 Dec 14. [18083778 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
- Gene Name:
- HTR6
- Uniprot ID:
- P50406
- Molecular Weight:
- 46953.625 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.065 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.14125 uM | Not Available | BindingDB 50020712 |
References
- Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW: Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem. 1996 Jan;66(1):47-56. [8522988 ]
- Sebben M, Ansanay H, Bockaert J, Dumuis A: 5-HT6 receptors positively coupled to adenylyl cyclase in striatal neurones in culture. Neuroreport. 1994 Dec 20;5(18):2553-7. [7696602 ]
- Hirst WD, Abrahamsen B, Blaney FE, Calver AR, Aloj L, Price GW, Medhurst AD: Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling. Mol Pharmacol. 2003 Dec;64(6):1295-308. [14645659 ]
- General Function:
- Thioesterase binding
- Specific Function:
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
- Gene Name:
- ADRA2A
- Uniprot ID:
- P08913
- Molecular Weight:
- 48956.275 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.114 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.69 uM | Not Available | BindingDB 50020712 |
References
- Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6. [14757140 ]
- Owens MJ, Morgan WN, Plott SJ, Nemeroff CB: Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther. 1997 Dec;283(3):1305-22. [9400006 ]
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Histamine receptor activity
- Specific Function:
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
- Gene Name:
- HRH1
- Uniprot ID:
- P35367
- Molecular Weight:
- 55783.61 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.00067 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.00095 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.00112 uM | Not Available | BindingDB 50020712 |
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. [6146381 ]
- von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
- General Function:
- Phosphatidylinositol phospholipase c activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM1
- Uniprot ID:
- P11229
- Molecular Weight:
- 51420.375 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.011 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.0147 uM | Not Available | BindingDB 50020712 |
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- Bymaster FP, Nelson DL, DeLapp NW, Falcone JF, Eckols K, Truex LL, Foreman MM, Lucaites VL, Calligaro DO: Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro. Schizophr Res. 1999 May 4;37(1):107-22. [10227113 ]
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- General Function:
- Receptor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM3
- Uniprot ID:
- P20309
- Molecular Weight:
- 66127.445 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.0128 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.039 uM | Not Available | BindingDB 50020712 |
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- Bymaster FP, Nelson DL, DeLapp NW, Falcone JF, Eckols K, Truex LL, Foreman MM, Lucaites VL, Calligaro DO: Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro. Schizophr Res. 1999 May 4;37(1):107-22. [10227113 ]
- General Function:
- Norepinephrine:sodium symporter activity
- Specific Function:
- Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name:
- SLC6A2
- Uniprot ID:
- P23975
- Molecular Weight:
- 69331.42 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.0133 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.019 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.035 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.063 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.102 uM | Not Available | BindingDB 50020712 |
References
- Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [14744476 ]
- Owens MJ, Morgan WN, Plott SJ, Nemeroff CB: Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther. 1997 Dec;283(3):1305-22. [9400006 ]
- Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]
- General Function:
- Protein heterodimerization activity
- Specific Function:
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
- Gene Name:
- ADRA1A
- Uniprot ID:
- P35348
- Molecular Weight:
- 51486.005 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [20363235 ]
- General Function:
- Histamine receptor activity
- Specific Function:
- The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity).
- Gene Name:
- HRH2
- Uniprot ID:
- P25021
- Molecular Weight:
- 40097.65 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 0.66 uM | Not Available | BindingDB 50020712 |
References
- Angus JA, Black JW: Pharmacological assay of cardiac H2-receptor blockade by amitriptyline and lysergic acid diethylamide. Circ Res. 1980 Jun;46(6 Pt 2):I64-9. [6103762 ]
- Quinones-Torrelo C, Sagrado S, Villanueva-Camanas RM, Medina-Hernandez MJ: Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography. J Med Chem. 1999 Aug 12;42(16):3154-62. [10447960 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
- Gene Name:
- OPRM1
- Uniprot ID:
- P35372
- Molecular Weight:
- 44778.855 Da
References
- Wahlstrom A, Lenhammar L, Ask B, Rane A: Tricyclic antidepressants inhibit opioid receptor binding in human brain and hepatic morphine glucuronidation. Pharmacol Toxicol. 1994 Jul;75(1):23-7. [7971731 ]
- Hamon M, Gozlan H, Bourgoin S, Benoliel JJ, Mauborgne A, Taquet H, Cesselin F, Mico JA: Opioid receptors and neuropeptides in the CNS in rats treated chronically with amoxapine or amitriptyline. Neuropharmacology. 1987 Jun;26(6):531-9. [3037421 ]
- General Function:
- G-protein coupled acetylcholine receptor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
- Gene Name:
- CHRM2
- Uniprot ID:
- P08172
- Molecular Weight:
- 51714.605 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.0096 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 0.0118 uM | Not Available | BindingDB 50020712 |
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- General Function:
- Guanyl-nucleotide exchange factor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
- Gene Name:
- CHRM4
- Uniprot ID:
- P08173
- Molecular Weight:
- 53048.65 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.0072 uM | Not Available | BindingDB 50020712 |
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- General Function:
- Opioid receptor activity
- Specific Function:
- Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
- Gene Name:
- SIGMAR1
- Uniprot ID:
- Q99720
- Molecular Weight:
- 25127.52 Da
References
- Villard V, Meunier J, Chevallier N, Maurice T: Pharmacological interaction with the sigma1 (sigma1)-receptor in the acute behavioral effects of antidepressants. J Pharmacol Sci. 2011;115(3):279-92. [21427517 ]
- Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [17689532 ]
- General Function:
- Monoamine transmembrane transporter activity
- Specific Function:
- Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name:
- SLC6A3
- Uniprot ID:
- Q01959
- Molecular Weight:
- 68494.255 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 2.58 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 3.25 uM | Not Available | BindingDB 50020712 |
| Inhibitory | 7.5 uM | Not Available | BindingDB 50020712 |
References
- Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [14744476 ]
- Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
- Gene Name:
- HTR1A
- Uniprot ID:
- P08908
- Molecular Weight:
- 46106.335 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.45 uM | Not Available | BindingDB 50020712 |
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
- Gene Name:
- HTR1B
- Uniprot ID:
- P28222
- Molecular Weight:
- 43567.535 Da
References
- Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [17689532 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.
- Gene Name:
- HTR1D
- Uniprot ID:
- P28221
- Molecular Weight:
- 41906.38 Da
References
- Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [17689532 ]
- General Function:
- Virus receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
- Gene Name:
- HTR2A
- Uniprot ID:
- P28223
- Molecular Weight:
- 52602.58 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
- Gene Name:
- HTR7
- Uniprot ID:
- P34969
- Molecular Weight:
- 53554.43 Da
References
- Lucchelli A, Santagostino-Barbone MG, D'Agostino G, Masoero E, Tonini M: The interaction of antidepressant drugs with enteric 5-HT7 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):284-9. [10997731 ]
- General Function:
- Protein heterodimerization activity
- Specific Function:
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
- Gene Name:
- ADRA1B
- Uniprot ID:
- P35368
- Molecular Weight:
- 56835.375 Da
References
- Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [20363235 ]
- General Function:
- Alpha1-adrenergic receptor activity
- Specific Function:
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
- Gene Name:
- ADRA1D
- Uniprot ID:
- P25100
- Molecular Weight:
- 60462.205 Da
References
- Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [20363235 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.
- Gene Name:
- NTRK2
- Uniprot ID:
- Q16620
- Molecular Weight:
- 91998.175 Da
References
- Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K: Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009 Jun 26;16(6):644-56. doi: 10.1016/j.chembiol.2009.05.010. [19549602 ]
25. Beta adrenergic receptor (Protein Group)
- General Function:
- Receptor signaling protein activity
- Specific Function:
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
- Included Proteins:
- P08588 , P07550 , P13945
References
- Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [17689532 ]
- General Function:
- G-protein coupled amine receptor activity
- Specific Function:
- Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
- Gene Name:
- DRD1
- Uniprot ID:
- P21728
- Molecular Weight:
- 49292.765 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.089 uM | Not Available | BindingDB 50020712 |
References
- von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
- General Function:
- G-protein coupled amine receptor activity
- Specific Function:
- Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
- Gene Name:
- DRD5
- Uniprot ID:
- P21918
- Molecular Weight:
- 52950.5 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.17 uM | Not Available | BindingDB 50020712 |
References
- von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name:
- DRD2
- Uniprot ID:
- P14416
- Molecular Weight:
- 50618.91 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.196 uM | Not Available | BindingDB 50020712 |
References
- von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
- General Function:
- G-protein coupled amine receptor activity
- Specific Function:
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
- Gene Name:
- DRD3
- Uniprot ID:
- P35462
- Molecular Weight:
- 44224.335 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.206 uM | Not Available | BindingDB 50020712 |
References
- von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
- General Function:
- Opioid receptor activity
- Specific Function:
- G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
- Gene Name:
- OPRD1
- Uniprot ID:
- P41143
- Molecular Weight:
- 40368.235 Da
References
- Onali P, Dedoni S, Olianas MC: Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):255-65. doi: 10.1124/jpet.109.159939. Epub 2009 Oct 14. [19828880 ]
- General Function:
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function:
- Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.Isoform TrkA-III is resistant to NGF, constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.
- Gene Name:
- NTRK1
- Uniprot ID:
- P04629
- Molecular Weight:
- 87496.465 Da
References
- Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K: Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009 Jun 26;16(6):644-56. doi: 10.1016/j.chembiol.2009.05.010. [19549602 ]
- General Function:
- Histamine receptor activity
- Specific Function:
- The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization.
- Gene Name:
- HRH3
- Uniprot ID:
- Q9Y5N1
- Molecular Weight:
- 48670.81 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | >1 uM | Not Available | BindingDB 50020712 |
References
- von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
- General Function:
- Histamine receptor activity
- Specific Function:
- The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
- Gene Name:
- HRH4
- Uniprot ID:
- Q9H3N8
- Molecular Weight:
- 44495.375 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| Inhibitory | 0.0336 uM | Not Available | BindingDB 50020712 |
References
- Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF: Discovery of a novel member of the histamine receptor family. Mol Pharmacol. 2001 Mar;59(3):427-33. [11179435 ]
- General Function:
- Opioid receptor activity
- Specific Function:
- G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
- Gene Name:
- OPRK1
- Uniprot ID:
- P41145
- Molecular Weight:
- 42644.665 Da
References
- Onali P, Dedoni S, Olianas MC: Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):255-65. doi: 10.1124/jpet.109.159939. Epub 2009 Oct 14. [19828880 ]
- General Function:
- Phosphatidylinositol phospholipase c activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM5
- Uniprot ID:
- P08912
- Molecular Weight:
- 60073.205 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:19903818). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12077175, PubMed:17156368). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:12077175, PubMed:17156368). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:19968958, PubMed:19307729, PubMed:19903818). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed:23903368, PubMed:19307729).
- Gene Name:
- KCNA1
- Uniprot ID:
- Q09470
- Molecular Weight:
- 56465.01 Da
References
- Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [17456683 ]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhytm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).
- Gene Name:
- KCND2
- Uniprot ID:
- Q9NZV8
- Molecular Weight:
- 70535.825 Da
References
- Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. [9781919 ]
- General Function:
- Metal ion binding
- Specific Function:
- Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.
- Gene Name:
- KCND3
- Uniprot ID:
- Q9UK17
- Molecular Weight:
- 73450.53 Da
References
- Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. [9781919 ]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine. Muscarinic agonist oxotremorine-M strongly suppress KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors.
- Gene Name:
- KCNQ2
- Uniprot ID:
- O43526
- Molecular Weight:
- 95846.575 Da
References
- Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [17456683 ]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs.
- Gene Name:
- KCNQ3
- Uniprot ID:
- O43525
- Molecular Weight:
- 96741.515 Da
References
- Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [17456683 ]
- General Function:
- Voltage-gated sodium channel activity
- Specific Function:
- Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
- Gene Name:
- SCN2A
- Uniprot ID:
- Q99250
- Molecular Weight:
- 227972.64 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 3.1 uM | Not Available | BindingDB 50020712 |
References
- Macsari I, Besidski Y, Csjernyik G, Nilsson LI, Sandberg L, Yngve U, Ahlin K, Bueters T, Eriksson AB, Lund PE, Venyike E, Oerther S, Hygge Blakeman K, Luo L, Arvidsson PI: 3-Oxoisoindoline-1-carboxamides: potent, state-dependent blockers of voltage-gated sodium channel Na(V)1.7 with efficacy in rat pain models. J Med Chem. 2012 Aug 9;55(15):6866-80. doi: 10.1021/jm300623u. Epub 2012 Jul 23. [22770500 ]
- General Function:
- Voltage-gated sodium channel activity involved in sa node cell action potential
- Specific Function:
- This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
- Gene Name:
- SCN5A
- Uniprot ID:
- Q14524
- Molecular Weight:
- 226937.475 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 1.6 uM | Not Available | BindingDB 50020712 |
References
- Macsari I, Besidski Y, Csjernyik G, Nilsson LI, Sandberg L, Yngve U, Ahlin K, Bueters T, Eriksson AB, Lund PE, Venyike E, Oerther S, Hygge Blakeman K, Luo L, Arvidsson PI: 3-Oxoisoindoline-1-carboxamides: potent, state-dependent blockers of voltage-gated sodium channel Na(V)1.7 with efficacy in rat pain models. J Med Chem. 2012 Aug 9;55(15):6866-80. doi: 10.1021/jm300623u. Epub 2012 Jul 23. [22770500 ]
- General Function:
- Voltage-gated sodium channel activity
- Specific Function:
- Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity).
- Gene Name:
- SCN9A
- Uniprot ID:
- Q15858
- Molecular Weight:
- 226370.175 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 1 uM | Not Available | BindingDB 50020712 |
| IC50 | 7 uM | Not Available | BindingDB 50020712 |
References
- Macsari I, Besidski Y, Csjernyik G, Nilsson LI, Sandberg L, Yngve U, Ahlin K, Bueters T, Eriksson AB, Lund PE, Venyike E, Oerther S, Hygge Blakeman K, Luo L, Arvidsson PI: 3-Oxoisoindoline-1-carboxamides: potent, state-dependent blockers of voltage-gated sodium channel Na(V)1.7 with efficacy in rat pain models. J Med Chem. 2012 Aug 9;55(15):6866-80. doi: 10.1021/jm300623u. Epub 2012 Jul 23. [22770500 ]
- General Function:
- Secondary active organic cation transmembrane transporter activity
- Specific Function:
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
- Gene Name:
- SLC22A1
- Uniprot ID:
- O15245
- Molecular Weight:
- 61153.345 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 16.9 uM | Not Available | BindingDB 50020712 |
References
- Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergstrom CA, Artursson P: Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1. J Med Chem. 2008 Oct 9;51(19):5932-42. doi: 10.1021/jm8003152. Epub 2008 Sep 13. [18788725 ]