T3DB: Fentanyl

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (5)XML

Targets (5)

Record Information

Version

2.0

Creation Date

2009-07-21 20:27:42 UTC

Update Date

2014-12-24 20:25:53 UTC

Accession Number

T3D2898

Identification

Common Name

Fentanyl

Class

Small Molecule

Description

A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)

Compound Type

Adjuvant
Adjuvant, Anesthesia
Amide
Amine
Analgesic
Analgesic, Opioid
Anesthetic
Anesthetic, Intravenous
Drug
Metabolite
Narcotic
Opiate Agonist
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
1-Phenethyl-4-(N-phenylpropionamido)piperidine
1-Phenethyl-4-N-propionylanilinopiperidine
Abstral
Actiq
Duragesic
Durogesic
Fentanest
Fentanil
Fentanila
Fentanilo
Fentanyl citrate
Fentanylum
Lazanda
N-(1-Phenethyl-4-piperidinyl)-N-phenylpropionamide
N-(1-Phenethyl-4-piperidyl)propionanilide
N-(1-Phenethyl-piperidin-4-yl)-N-phenyl-propionamide
N-(1-Phenethylpiperidin-4-yl)-N-phenylpropionamide
N-Phenethyl-4-(N-propionylanilino)piperidine
N-Phenyl-N-(1-(2-phenylethyl)-4-piperidinyl)propanamide
Nasalfent
Phentanyl
Rapinyl
Subsys

Chemical Formula

C₂₂H₂₈N₂O

Average Molecular Mass

336.471 g/mol

Monoisotopic Mass

336.220 g/mol

CAS Registry Number

437-38-7

IUPAC Name

N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide

Traditional Name

fentanyl

SMILES

CCC(=O)N(C1CCN(CCC2=CC=CC=C2)CC1)C1=CC=CC=C1

InChI Identifier

InChI=1S/C22H28N2O/c1-2-22(25)24(20-11-7-4-8-12-20)21-14-17-23(18-15-21)16-13-19-9-5-3-6-10-19/h3-12,21H,2,13-18H2,1H3

InChI Key

InChIKey=PJMPHNIQZUBGLI-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as fentanyls. Fentanyls are compounds containing the fentanyl moiety or a derivative, which is based on a N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylpropanamide skeleton.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Piperidines

Sub Class

Fentanyls

Direct Parent

Fentanyls

Alternative Parents

Substituents

Fentanyl
Phenethylamine
Anilide
Aralkylamine
Monocyclic benzene moiety
Benzenoid
Tertiary carboxylic acid amide
Amino acid or derivatives
Carboxamide group
Tertiary amine
Tertiary aliphatic amine
Carboxylic acid derivative
Azacycle
Organopnictogen compound
Organooxygen compound
Organonitrogen compound
Organic oxygen compound
Amine
Carbonyl group
Organic oxide
Organic nitrogen compound
Hydrocarbon derivative
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

piperidines (CHEBI:119915 )
monocarboxylic acid amide (CHEBI:119915 )
anilide (CHEBI:119915 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	87.5°C
Boiling Point	Not Available
Solubility	200 mg/L (at 25°C)
LogP	4.05

Predicted Properties

Property	Value	Source
Water Solubility	0.024 g/L	ALOGPS
logP	4.12	ALOGPS
logP	3.82	ChemAxon
logS	-4.2	ALOGPS
pKa (Strongest Basic)	8.77	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	23.55 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	103.48 m³·mol⁻¹	ChemAxon
Polarizability	40.03 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-000i-5930000000-f7e6ba23728816e17e78	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-000i-0009000000-62593b54c6285a566893	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-000i-0209000000-d550d803c25d31570227	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-000i-0901000000-09bd125eea134f8811a4	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-000i-0900000000-2c34993eade063cb426f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-001r-0900000000-beb72ea99dc9c125d29b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-000i-0009000000-bf70e4d857c26d30032f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-000i-0907000000-a9f5d0c422eff1474d38	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-000i-0900000000-0c03ba9ef576114a9503	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0a4i-0900000000-d2a36b402c3a7424fab6	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0a4i-1900000000-e0cbdfad80c306baabc1	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0a4i-2900000000-ea551550ac6cbe6d3960	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0pdi-8900000000-89b1a77e558ec74cf3ac	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0kdj-9400000000-358833c028a079789d0b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0ufs-9200000000-ff2c211a084a5f124781	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-000i-0900000000-da874163fadaa39d25ad	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-000i-0901000000-09bd125eea134f8811a4	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-000i-0009000000-e126a8d88c9106409cac	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-000i-0209000000-d550d803c25d31570227	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-001r-0900000000-2ed12cf85c72a16b8cdb	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-1239000000-6f316602b5d12ff1b1b9	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a4r-4942000000-703ee8a328127a82245c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-4900000000-c38eaa80ecf3e4334782	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0009000000-303253b936dc7fea5dd0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0550-3498000000-cbae1ca8da3e5b395fa4	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-05dl-6930000000-8603b3c4374827ab0621	2016-08-03	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0002-9850000000-7ce3a6f35f5dee98185f	2014-09-20	View Spectrum

Toxicity Profile

Route of Exposure

Epidural; parental (transdermal, intramuscular).

Mechanism of Toxicity

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Fentanyl's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hypopolarization and reduced neuronal excitability.

Metabolism

Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system. Route of Elimination: Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system and mostly eliminated in urine. Within 72 hours of IV fentanyl administration, approximately 75% of the dose is excreted in urine, mostly as metabolites with less than 10% representing unchanged drug. Half Life: 7 hours (range 3-12)

Toxicity Values

LD50: 3.1 mg/kg (rat) LD50: 0.03 mg/kg (monkeys)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the treatment of cancer patients with severe pain that breaks through their regular narcotic therapy. Used as an inhalation anesthetic. (6)

Minimum Risk Level

Not Available

Health Effects

Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.

Symptoms

More common symptoms are dizziness, light-headedness, or feeling faint; drowsiness; nausea or vomiting; unusual tiredness or weakness. Less common or rare ones are blurred or double vision or other vision problems; confusion; constipation; convulsions (seizures); difficult or painful urination; mental depression; shortness of breath, trouble in breathing, tightness in the chest, or wheezing; skin rash, hives, or itching; unusual excitement (6)

Treatment

For the management of hypoventilation, immediate countermeasures include removing the Fentanyl and physically or verbally stimulating the patient. These actions can be followed by administration of a specific narcotic antagonist such as naloxone. The duration of hypoventilation following an overdose may be longer than the effects of the narcotic antagonist's action (the half-life of naloxone ranges from 30 to 81 minutes). The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after system removal; repeated administration of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and the release of catecholamines. Always ensure a patent airway is established and maintained, administer oxygen and assist or control respiration as indicated and use an oropharyngeal airway or endotracheal tube if necessary. Adequate body temperature and fluid intake should be maintained. (8)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

119915

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Fentanyl

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Fentanyl

References

Synthesis Reference

Mark Rubino, “Process of making fentanyl intermediates.” U.S. Patent US20060100438, issued May 11, 2006.

MSDS

Link

General References

Van Bever WF, Niemegeers CJ, Janssen PA: Synthetic analgesics. Synthesis and pharmacology of the diastereoisomers of N-(3-methyl-1-(2-phenylethyl)-4-piperidyl)-N-phenylpropanamide and N-(3-methyl-1-(1-methyl-2-phenylethyl)-4-piperidyl)-N-phenylpropanamide. J Med Chem. 1974 Oct;17(10):1047-51. [4420811 ]
Messina J, Darwish M, Fine PG: Fentanyl buccal tablet. Drugs Today (Barc). 2008 Jan;44(1):41-54. doi: 10.1358/dot.2008.44.1.1178469. [18301803 ]
Taylor DR: Fentanyl buccal tablet: rapid relief from breakthrough pain. Expert Opin Pharmacother. 2007 Dec;8(17):3043-51. [18001263 ]
Simpson DM, Messina J, Xie F, Hale M: Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2007 Apr;29(4):588-601. [17617282 ]
Martindale. The Extra Pharmacopoeia, 30th ed.
Drugs.com [Link]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Down-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Targets

Target Details

1. Mu-type opioid receptor

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0029 uM	Not Available	BindingDB 50008984
Inhibitory	0.00397 uM	Not Available	BindingDB 50008984
Inhibitory	0.00845 uM	Not Available	BindingDB 50008984
IC50	0.0013 uM	Not Available	BindingDB 50008984
IC50	0.0031 uM	Not Available	BindingDB 50008984

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
You HJ, Colpaert FC, Arendt-Nielsen L: The novel analgesic and high-efficacy 5-HT1A receptor agonist F 13640 inhibits nociceptive responses, wind-up, and after-discharges in spinal neurons and withdrawal reflexes. Exp Neurol. 2005 Jan;191(1):174-83. [15589524 ]
Scott LJ, Perry CM: Remifentanil: a review of its use during the induction and maintenance of general anaesthesia. Drugs. 2005;65(13):1793-823. [16114980 ]
Scott LJ, Perry CM: Spotlight on remifentanil for general anaesthesia. CNS Drugs. 2005;19(12):1069-74. [16332149 ]
Dosen-Micovic L, Ivanovic M, Micovic V: Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor. Bioorg Med Chem. 2006 May 1;14(9):2887-95. Epub 2006 Jan 11. [16376082 ]
Dardonville C, Fernandez-Fernandez C, Gibbons SL, Ryan GJ, Jagerovic N, Gabilondo AM, Meana JJ, Callado LF: Synthesis and pharmacological studies of new hybrid derivatives of fentanyl active at the mu-opioid receptor and I2-imidazoline binding sites. Bioorg Med Chem. 2006 Oct 1;14(19):6570-80. Epub 2006 Jun 23. [16797997 ]
Poulain R, Horvath D, Bonnet B, Eckhoff C, Chapelain B, Bodinier MC, Deprez B: From hit to lead. Combining two complementary methods for focused library design. Application to mu opiate ligands. J Med Chem. 2001 Oct 11;44(21):3378-90. [11585443 ]
Bagley JR, Thomas SA, Rudo FG, Spencer HK, Doorley BM, Ossipov MH, Jerussi TP, Benvenga MJ, Spaulding T: New 1-(heterocyclylalkyl)-4-(propionanilido)-4-piperidinyl methyl ester and methylene methyl ether analgesics. J Med Chem. 1991 Feb;34(2):827-41. [1847432 ]
Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Dardonville C, Jagerovic N, Callado LF, Meana JJ: Fentanyl derivatives bearing aliphatic alkaneguanidinium moieties: a new series of hybrid molecules with significant binding affinity for mu-opioid receptors and I2-imidazoline binding sites. Bioorg Med Chem Lett. 2004 Jan 19;14(2):491-3. [14698188 ]
Subramanian G, Paterlini MG, Portoghese PS, Ferguson DM: Molecular docking reveals a novel binding site model for fentanyl at the mu-opioid receptor. J Med Chem. 2000 Feb 10;43(3):381-91. [10669565 ]
Wang C, McFadyen IJ, Traynor JR, Mosberg HI: Design of a high affinity peptidomimetic opioid agonist from peptide pharmacophore models. Bioorg Med Chem Lett. 1998 Oct 6;8(19):2685-8. [9873603 ]

Target Details

2. Kappa-type opioid receptor

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0848 uM	Not Available	BindingDB 50008984
Inhibitory	0.1965 uM	Not Available	BindingDB 50008984
Inhibitory	0.197 uM	Not Available	BindingDB 50008984
Inhibitory	0.255 uM	Not Available	BindingDB 50008984
Inhibitory	1.13 uM	Not Available	BindingDB 50008984
IC50	1.58 uM	Not Available	BindingDB 50008984
IC50	5.893 uM	Not Available	BindingDB 50008984

References

Pascoe JE, Williams KL, Mukhopadhyay P, Rice KC, Woods JH, Ko MC: Effects of mu, kappa, and delta opioid receptor agonists on the function of hypothalamic-pituitary-adrenal axis in monkeys. Psychoneuroendocrinology. 2008 May;33(4):478-86. doi: 10.1016/j.psyneuen.2008.01.006. Epub 2008 Mar 5. [18325678 ]
Poulain R, Horvath D, Bonnet B, Eckhoff C, Chapelain B, Bodinier MC, Deprez B: From hit to lead. Combining two complementary methods for focused library design. Application to mu opiate ligands. J Med Chem. 2001 Oct 11;44(21):3378-90. [11585443 ]
Bagley JR, Thomas SA, Rudo FG, Spencer HK, Doorley BM, Ossipov MH, Jerussi TP, Benvenga MJ, Spaulding T: New 1-(heterocyclylalkyl)-4-(propionanilido)-4-piperidinyl methyl ester and methylene methyl ether analgesics. J Med Chem. 1991 Feb;34(2):827-41. [1847432 ]
Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
Subramanian G, Paterlini MG, Portoghese PS, Ferguson DM: Molecular docking reveals a novel binding site model for fentanyl at the mu-opioid receptor. J Med Chem. 2000 Feb 10;43(3):381-91. [10669565 ]
Brine GA, Stark PA, Liu Y, Carroll FI, Singh P, Xu H, Rothman RB: Enantiomers of diastereomeric cis-N-[1-(2-hydroxy-2-phenylethyl)- 3-methyl-4-piperidyl]-N-phenylpropanamides: synthesis, X-ray analysis, and biological activities. J Med Chem. 1995 Apr 28;38(9):1547-57. [7739013 ]
Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell GI, Reisine T: Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 1994 Feb;45(2):330-4. [8114680 ]
Wang C, McFadyen IJ, Traynor JR, Mosberg HI: Design of a high affinity peptidomimetic opioid agonist from peptide pharmacophore models. Bioorg Med Chem Lett. 1998 Oct 6;8(19):2685-8. [9873603 ]

Target Details

3. Delta-type opioid receptor

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.1527 uM	Not Available	BindingDB 50008984
Inhibitory	1 uM	Not Available	BindingDB 50008984

References

Rodrigues AR, Castro MS, Francischi JN, Perez AC, Duarte ID: Participation of ATP-sensitive K+ channels in the peripheral antinociceptive effect of fentanyl in rats. Braz J Med Biol Res. 2005 Jan;38(1):91-7. Epub 2005 Jan 18. [15665994 ]
Poonawala T, Levay-Young BK, Hebbel RP, Gupta K: Opioids heal ischemic wounds in the rat. Wound Repair Regen. 2005 Mar-Apr;13(2):165-74. [15828941 ]
Sahin AS, Duman A, Atalik EK, Ogun CO, Sahin TK, Erol A, Ozergin U: The mechanisms of the direct vascular effects of fentanyl on isolated human saphenous veins in vitro. J Cardiothorac Vasc Anesth. 2005 Apr;19(2):197-200. [15868528 ]
Darwish M, Tempero K, Kirby M, Thompson J: Pharmacokinetics and dose proportionality of fentanyl effervescent buccal tablets in healthy volunteers. Clin Pharmacokinet. 2005;44(12):1279-86. [16372825 ]
Darwish M, Kirby M, Robertson P Jr, Tracewell W, Jiang JG: Pharmacokinetic properties of fentanyl effervescent buccal tablets: a phase I, open-label, crossover study of single-dose 100, 200, 400, and 800 microg in healthy adult volunteers. Clin Ther. 2006 May;28(5):707-14. [16861092 ]
Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell GI, Reisine T: Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 1994 Feb;45(2):330-4. [8114680 ]

Target Details

4. Multidrug resistance protein 1

General Function:: Xenobiotic-transporting atpase activity
Specific Function:: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:: ABCB1
Uniprot ID:: P08183
Molecular Weight:: 141477.255 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	6.5 uM	Not Available	BindingDB 50008984

References

Wandel C, Kim R, Wood M, Wood A: Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein. Anesthesiology. 2002 Apr;96(4):913-20. [11964599 ]

Target Details

5. Potassium voltage-gated channel subfamily H member 2

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	1.8197 uM	Not Available	BindingDB 50008984

References

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 ]

Fentanyl (T3D2898)

Structure for T3D2898: Fentanyl

Targets

Binding/Activity Constants

References

Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

References