Maprotiline (T3D2934)

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

References

1. Saba W, Valette H, Schollhorn-Peyronneau MA, Coulon C, Ottaviani M, Chalon S, Dolle F, Emond P, Halldin C, Helfenbein J, Madelmont JC, Deloye JB, Guilloteau D, Bottlaender M: [11C]LBT-999: a suitable radioligand for investigation of extra-striatal dopamine transporter with PET. Synapse. 2007 Jan;61(1):17-23. [17068778 ]
2. Arai S, Morita K, Kitayama S, Kumagai K, Kumagai M, Kihira K, Dohi T: Chronic inhibition of the norepinephrine transporter in the brain participates in seizure sensitization to cocaine and local anesthetics. Brain Res. 2003 Feb 21;964(1):83-90. [12573515 ]
3. 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 ]
4. Heffernan GD, Coghlan RD, Manas ES, McDevitt RE, Li Y, Mahaney PE, Robichaud AJ, Huselton C, Alfinito P, Bray JA, Cosmi SA, Johnston GH, Kenney T, Koury E, Winneker RC, Deecher DC, Trybulski EJ: Dual acting norepinephrine reuptake inhibitors and 5-HT(2A) receptor antagonists: Identification, synthesis and activity of novel 4-aminoethyl-3-(phenylsulfonyl)-1H-indoles. Bioorg Med Chem. 2009 Nov 15;17(22):7802-15. doi: 10.1016/j.bmc.2009.09.023. Epub 2009 Sep 18. [19836247 ]

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

References

1. Noguchi S, Inukai T, Kuno T, Tanaka C: The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking. Physiol Behav. 1992 Jun;51(6):1123-7. [1353628 ]
2. Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. [6146381 ]
3. 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

References

1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [6297650 ]
2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [7052344 ]
3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [6118411 ]

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

References

1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [6297650 ]
2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [7052344 ]
3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [6118411 ]

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

References

1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [6297650 ]
2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [7052344 ]
3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [6118411 ]

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

References

1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [6297650 ]
2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [7052344 ]
3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [6118411 ]

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

1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [6297650 ]
2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [7052344 ]
3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [6118411 ]

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.

Included Proteins:

P35348 , P35368 , P25100

References

1. Buckley NA, McManus PR: Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data? Drug Saf. 1998 May;18(5):369-81. [9589848 ]
2. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [6086881 ]

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

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

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

1. Peroutka SJ, Lebovitz RM, Snyder SH: Two distinct central serotonin receptors with different physiological functions. Science. 1981 May 15;212(4496):827-9. [7221567 ]

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

References

1. Peroutka SJ, Lebovitz RM, Snyder SH: Two distinct central serotonin receptors with different physiological functions. Science. 1981 May 15;212(4496):827-9. [7221567 ]

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

1. 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:

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.

Included Proteins:

P08913 , P18089 , P18825

References

1. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [6086881 ]

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

References

1. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [6086881 ]

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

References

1. 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: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

References

1. 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:

Primary amine oxidase activity

Specific Function:

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.

Gene Name:

MAOB

Uniprot ID:

P27338

Molecular Weight:

58762.475 Da