Identification

Name
Cocaine
Accession Number
DB00907  (APRD00080)
Type
Small Molecule
Groups
Approved, Illicit
Description

An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.

Structure
Thumb
Synonyms
  • (-)-Cocaine
  • (−)-cocaine
  • [1R-(exo,exo)]-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid, methyl ester
  • 2-methyl-3β-hydroxy-1αH,5αH-tropane-2β-carboxylate benzoate (ester)
  • Benzoylmethylecgonine
  • beta-Cocain
  • Cocain
  • Cocaina
  • Cocainum
  • Kokain
  • L-Cocain
  • L-Cocaine
  • methyl [1R-(exo,exo)]-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
  • Methyl benzoylecgonine
  • Neurocaine
External IDs
IDS-NC-004 / RX-0041 / RX0041
Product Ingredients
IngredientUNIICASInChI Key
Cocaine hydrochlorideXH8T8T6WZH53-21-4PIQVDUKEQYOJNR-VZXSFKIWSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cocaine Hydrochloride Top Sol 40mg/mlLiquid40 mgTopicalSandoz Canada Incorporated1992-12-31Not applicableCanada
Cocaine Hydrochloride Topical Sol 10%Liquid100 mgTopicalSandoz Canada Incorporated1992-12-31Not applicableCanada
GopreltoSolution40 mg/1mLNasalGenus Lifesciences Inc.2018-01-08Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cocaine HydrochlorideSolution40 mg/1mLNasalGenus Lifesciences Inc.2018-06-04Not applicableUs
PMS-cocaine Hydrochloride Topical Sol 10%Liquid100 mgTopicalPharmascience Inc1995-12-31Not applicableCanada
PMS-cocaine Hydrochloride Topical Sol 4%Liquid40 mgTopicalPharmascience Inc1997-03-17Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Cocaine HydrochlorideCocaine hydrochloride (40 mg/1mL)SolutionTopicalLannett Company, Inc.2008-12-01Not applicableUs
Cocaine HydrochlorideCocaine hydrochloride (100 mg/1mL)SolutionTopicalLannett Company, Inc.2008-12-01Not applicableUs
Categories
UNII
I5Y540LHVR
CAS number
50-36-2
Weight
Average: 303.3529
Monoisotopic: 303.147058165
Chemical Formula
C17H21NO4
InChI Key
ZPUCINDJVBIVPJ-LJISPDSOSA-N
InChI
InChI=1S/C17H21NO4/c1-18-12-8-9-13(18)15(17(20)21-2)14(10-12)22-16(19)11-6-4-3-5-7-11/h3-7,12-15H,8-10H2,1-2H3/t12-,13+,14-,15+/m0/s1
IUPAC Name
methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
SMILES
[H][C@]12CC[C@]([H])([C@H]([C@H](C1)OC(=O)C1=CC=CC=C1)C(=O)OC)N2C

Pharmacology

Indication

For the introduction of local (topical) anesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities.

Pharmacodynamics

Cocaine is a local anesthetic indicated for the introduction of local (topical) anesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities.

Mechanism of action

Cocaine produces anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels. Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. Cocaine is the only local anesthetic with vasoconstrictive properties. This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. Its effect on dopamine levels is most responsible for the addictive property of cocaine.

TargetActionsOrganism
ASodium-dependent dopamine transporter
inhibitor
Human
ASodium-dependent noradrenaline transporter
inhibitor
Human
ASodium-dependent serotonin transporter
inhibitor
Human
ASodium channel protein type 5 subunit alpha
inhibitor
Human
USodium channel protein type 11 subunit alpha
inhibitor
Human
USodium channel protein type 10 subunit alpha
inhibitor
Human
UMuscarinic acetylcholine receptor M1
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
USigma non-opioid intracellular receptor 1Not AvailableHuman
ULiver carboxylesterase 1Not AvailableHuman
Absorption

Cocaine is absorbed from all sites of application, including mucous membranes and gastrointestinal mucosa. By oral or intra-nasal route, 60 to 80% of cocaine is absorbed.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic. Cocaine is metabolized to benzoylecgonine and ecgonine methyl ester, which are both excreted in the urine. In the presence of alcohol, a further active metabolite, cocaethylene is formed, and is more toxic then cocaine itself.

Route of elimination
Not Available
Half life

1 hour

Clearance
Not Available
Toxicity

Intense agitation, convulsions, hypertension, rhythm disturbance, coronary insufficiency, hyperthermia, rhabdomyolysis, and renal impairment. Oral mouse LD50 = 96 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Cocaine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AclidiniumThe risk or severity of adverse effects can be increased when Cocaine is combined with Aclidinium.
AgmatineThe risk or severity of adverse effects can be increased when Cocaine is combined with Agmatine.
Ajulemic acidCocaine may increase the tachycardic activities of Ajulemic acid.
AlcuroniumThe risk or severity of adverse effects can be increased when Cocaine is combined with Alcuronium.
AmantadineThe risk or severity of adverse effects can be increased when Cocaine is combined with Amantadine.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Cocaine.
AmobarbitalThe risk or severity of adverse effects can be increased when Cocaine is combined with Amobarbital.
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Cocaine.
Anisotropine MethylbromideThe risk or severity of adverse effects can be increased when Anisotropine Methylbromide is combined with Cocaine.
AprobarbitalThe risk or severity of adverse effects can be increased when Cocaine is combined with Aprobarbital.
Food Interactions
Not Available

References

Synthesis Reference

Nobuyuki Shigetoh, Hiroshi Nakayama, Jinsei Miyazaki, Tadayasu Mitsumata, "Labelling colors for detecting cocaine or methamphetamine, method of preparing the same and detector for cocaine or methamphetamine." U.S. Patent US5571727, issued October, 1981.

US5571727
General References
  1. Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT: Cocaine in herbal tea. JAMA. 1986 Jan 3;255(1):40. [PubMed:3940302]
  2. Volkow ND, Wang GJ, Fischman MW, Foltin R, Fowler JS, Franceschi D, Franceschi M, Logan J, Gatley SJ, Wong C, Ding YS, Hitzemann R, Pappas N: Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain. Life Sci. 2000 Aug 11;67(12):1507-15. [PubMed:10983846]
  3. Dimitrijevic N, Dzitoyeva S, Manev H: An automated assay of the behavioral effects of cocaine injections in adult Drosophila. J Neurosci Methods. 2004 Aug 30;137(2):181-4. [PubMed:15262059]
  4. Uz T, Akhisaroglu M, Ahmed R, Manev H: The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice. Neuropsychopharmacology. 2003 Dec;28(12):2117-23. [PubMed:12865893]
  5. McClung CA, Sidiropoulou K, Vitaterna M, Takahashi JS, White FJ, Cooper DC, Nestler EJ: Regulation of dopaminergic transmission and cocaine reward by the Clock gene. Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9377-81. Epub 2005 Jun 20. [PubMed:15967985]
External Links
Human Metabolome Database
HMDB0015043
KEGG Drug
D00110
KEGG Compound
C01416
PubChem Compound
446220
PubChem Substance
46506326
ChemSpider
10194104
BindingDB
22418
ChEBI
27958
ChEMBL
CHEMBL370805
Therapeutic Targets Database
DAP000834
PharmGKB
PA449072
IUPHAR
2286
Guide to Pharmacology
GtP Drug Page
HET
COC
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cocaine
ATC Codes
N01BC01 — CocaineS01HA01 — CocaineR02AD03 — CocaineS02DA02 — Cocaine
PDB Entries
1i7z / 1q72 / 2ajv / 2pgz / 4xp4 / 4xpb
MSDS
Download (104 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceActive Cocaine Users1
0CompletedBasic ScienceCocaine Abuse / Dependence, Cocaine1
0CompletedBasic ScienceCocaine Use Disorders1
0CompletedBasic ScienceDependence, Cocaine1
0RecruitingBasic ScienceCocaine Use Disorders1
1Active Not RecruitingBasic ScienceCocaine Dependent Subjects1
1CompletedBasic ScienceCocaine Use Disorders1
1CompletedDiagnosticCocaine Abuse1
1CompletedDiagnosticCocaine Use / Pharmacokinetics1
1CompletedTreatmentCocaine Use Disorders1
1CompletedTreatmentCocaine-Related Disorders3
1CompletedTreatmentHealthy Volunteers1
1RecruitingBasic ScienceCocaine Use Disorders2
1RecruitingOtherDependence, Cocaine2
1RecruitingTreatmentCocaine Abuse / Cocaine-Related Disorders / Dependence, Cocaine1
1RecruitingTreatmentDependence, Cocaine1
1Unknown StatusNot AvailableCocaine-Related Disorders1
1Unknown StatusTreatmentCocaine Induced Sympathoexciation and Vasoconstriction1
1, 2CompletedNot AvailableDependence, Cocaine1
1, 2CompletedTreatmentDependence, Cocaine1
2CompletedTreatmentCocaine Abuse1
2CompletedTreatmentDependence, Cocaine1
2CompletedTreatmentDependence, Cocaine / Opioid Dependence / Opioid Related Disorders1
2TerminatedTreatmentDependence, Cocaine1
3CompletedTreatmentAny Ear Nose or Throat Conditions / Any Ear, Nose or Throat Condition With the Identified Need for a Diagnostic Procedure or Surgery on or Through the Mucous Membranes of the Nasal Cavities / With Identified Need for a Diagnostic Procedure or Surgery on or Through the Mucous Membranes of the Nasal Cavities1
3TerminatedTreatmentDiagnostic / Of the Nasal Cavities / Procedures and Surgeries on or Through Accessible Mucous Membranes1
4Unknown StatusNot AvailableChronic Rhinosinusitis1
4WithdrawnTreatmentCocaine-Related Disorders1
Not AvailableActive Not RecruitingOtherDependence, Cocaine1
Not AvailableActive Not RecruitingOtherDependence, Cocaine / Impulsivity1
Not AvailableCompletedNot AvailableDependence, Cocaine1
Not AvailableCompletedTreatmentAge-Related Macular Degeneration (AMD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Cody Laboratories Inc.
  • Lannett Co. Inc.
  • Mallinckrodt Inc.
  • Roxane Labs
Dosage forms
FormRouteStrength
SolutionTopical100 mg/1mL
SolutionTopical40 mg/1mL
LiquidTopical40 mg
LiquidTopical100 mg
SolutionNasal40 mg/1mL
Prices
Unit descriptionCostUnit
Cocaine hydrochloride powder68.44USD g
Cocaine 10% solution10.68USD ml
Cocaine 4% solution6.22USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9867815No2017-02-072037-02-07Us
US10016407No2017-02-072037-02-07Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)98 °CPhysProp
water solubility1800 mg/L (at 22 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.30HANSCH,C ET AL. (1995)
logS-2.23ADME Research, USCD
pKa8.61 (at 15 °C)MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility5.03 mg/mLALOGPS
logP1.97ALOGPS
logP2.28ChemAxon
logS-1.8ALOGPS
pKa (Strongest Basic)8.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area55.84 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity81.16 m3·mol-1ChemAxon
Polarizability32.36 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8644
Blood Brain Barrier+0.8805
Caco-2 permeable+0.7654
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor IInhibitor0.8168
P-glycoprotein inhibitor IINon-inhibitor0.893
Renal organic cation transporterInhibitor0.6182
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6856
CYP450 1A2 substrateNon-inhibitor0.8627
CYP450 2C9 inhibitorNon-inhibitor0.9341
CYP450 2D6 inhibitorNon-inhibitor0.5614
CYP450 2C19 inhibitorNon-inhibitor0.9383
CYP450 3A4 inhibitorNon-inhibitor0.9237
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9408
Ames testNon AMES toxic0.7437
CarcinogenicityNon-carcinogens0.9585
BiodegradationNot ready biodegradable0.5319
Rat acute toxicity2.6387 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8463
hERG inhibition (predictor II)Non-inhibitor0.8042
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (2.96 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-001i-9200000000-5262d40bbcdec08759ab
GC-MS Spectrum - CI-BGC-MSsplash10-0udi-0109000000-319d789d066a157a0966
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0009000000-a2004e33ce1140fd0ed1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0f89-0908000000-b5abe87da56f09f21f65
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0900000000-ee9c7f3b491476f49e98
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0900000000-2dab4b98f61ec4ba2467
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0fz9-0900000000-b3c61e257fbaf700b52b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0900000000-3b1dc1a8c8390bfb6c3e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-0479d3211208134ed140
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0ue9-0709000000-d19680d406708cbbc59b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-1900000000-5ac8f8a2719f70332b86
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-3900000000-5ff2f6c28b5db03035be
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-053r-8900000000-e597f9f6f5014d501e62
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a5c-9500000000-0fcf099229f148719078
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-ee11934dd1158606bb84
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0ue9-0609000000-bd90cd1f98ce1845ba6b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-1900000000-9fc49ca16ab794b8c37d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-3900000000-cb0b593e7f379f7c6aef
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-053r-8900000000-2a88bad614aed29eac52
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a59-9500000000-c9713abdcf52a45d6ed2
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0900000000-c18cf276038cf1946f20

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Benzoic acid esters
Alternative Parents
Tropane alkaloids / Piperidinecarboxylic acids / Benzoyl derivatives / N-alkylpyrrolidines / Dicarboxylic acids and derivatives / Methyl esters / Trialkylamines / Amino acids and derivatives / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Benzoate ester / Piperidinecarboxylic acid / Tropane alkaloid / Benzoyl / Dicarboxylic acid or derivatives / Piperidine / N-alkylpyrrolidine / Methyl ester / Pyrrolidine / Amino acid or derivatives
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, tropane alkaloid, methyl ester, benzoate ester (CHEBI:27958) / Tropane alkaloids, Alkaloids (C01416)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Wilson JM, Levey AI, Bergeron C, Kalasinsky K, Ang L, Peretti F, Adams VI, Smialek J, Anderson WR, Shannak K, Deck J, Niznik HB, Kish SJ: Striatal dopamine, dopamine transporter, and vesicular monoamine transporter in chronic cocaine users. Ann Neurol. 1996 Sep;40(3):428-39. [PubMed:8797532]
  2. Kim DI, Schweri MM, Deutsch HM: Synthesis and pharmacology of site specific cocaine abuse treatment agents: 8-substituted isotropane (3-azabicyclo[3.2.1]octane) dopamine uptake inhibitors. J Med Chem. 2003 Apr 10;46(8):1456-64. [PubMed:12672245]
  3. Rothman RB, Baumann MH, Dersch CM, Appel J, Houghten RA: Discovery of novel peptidic dopamine transporter ligands by screening a positional scanning combinatorial hexapeptide library. Synapse. 1999 Sep 1;33(3):239-46. [PubMed:10420171]
  4. Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [PubMed:15351386]
  5. 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. [PubMed:9537821]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Galli A, DeFelice LJ, Duke BJ, Moore KR, Blakely RD: Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants. J Exp Biol. 1995 Oct;198(Pt 10):2197-212. [PubMed:7500004]
  2. Burchett SA, Bannon MJ: Serotonin, dopamine and norepinephrine transporter mRNAs: heterogeneity of distribution and response to 'binge' cocaine administration. Brain Res Mol Brain Res. 1997 Oct 3;49(1-2):95-102. [PubMed:9387868]
  3. Zhao Y, Sun L: Perinatal cocaine exposure reduces myocardial norepinephrine transporter function in the neonatal rat. Neurotoxicol Teratol. 2004 May-Jun;26(3):443-50. [PubMed:15113605]
  4. Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [PubMed:15351386]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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 t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Patkar AA, Berrettini WH, Hoehe M, Thornton CC, Gottheil E, Hill K, Weinstein SP: Serotonin transporter polymorphisms and measures of impulsivity, aggression, and sensation seeking among African-American cocaine-dependent individuals. Psychiatry Res. 2002 Jun 1;110(2):103-15. [PubMed:12057823]
  2. Barker EL, Moore KR, Rakhshan F, Blakely RD: Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter. J Neurosci. 1999 Jun 15;19(12):4705-17. [PubMed:10366604]
  3. Corey JL, Quick MW, Davidson N, Lester HA, Guastella J: A cocaine-sensitive Drosophila serotonin transporter: cloning, expression, and electrophysiological characterization. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1188-92. [PubMed:8302852]
  4. Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [PubMed:15351386]
  5. 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. [PubMed:9537821]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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 pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Antzelevitch C: Brugada syndrome. Pacing Clin Electrophysiol. 2006 Oct;29(10):1130-59. [PubMed:17038146]
  2. Satish OS, Yeh KH, Wen MS: Brugada syndrome--an update. Chang Gung Med J. 2005 Feb;28(2):69-76. [PubMed:15880981]
  3. Wright SN, Wang SY, Xiao YF, Wang GK: State-dependent cocaine block of sodium channel isoforms, chimeras, and channels coexpressed with the beta1 subunit. Biophys J. 1999 Jan;76(1 Pt 1):233-45. [PubMed:9876137]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity
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 pr...
Gene Name
SCN11A
Uniprot ID
Q9UI33
Uniprot Name
Sodium channel protein type 11 subunit alpha
Molecular Weight
204919.66 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. [PubMed: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. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity
Specific Function
Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference acro...
Gene Name
SCN10A
Uniprot ID
Q9Y5Y9
Uniprot Name
Sodium channel protein type 10 subunit alpha
Molecular Weight
220623.605 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. [PubMed: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. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [PubMed:15351386]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [PubMed:15351386]
  2. Sharkey J, Ritz MC, Schenden JA, Hanson RC, Kuhar MJ: Cocaine inhibits muscarinic cholinergic receptors in heart and brain. J Pharmacol Exp Ther. 1988 Sep;246(3):1048-52. [PubMed:3047364]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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 m...
Gene Name
SIGMAR1
Uniprot ID
Q99720
Uniprot Name
Sigma non-opioid intracellular receptor 1
Molecular Weight
25127.52 Da
References
  1. Navarro G, Moreno E, Aymerich M, Marcellino D, McCormick PJ, Mallol J, Cortes A, Casado V, Canela EI, Ortiz J, Fuxe K, Lluis C, Ferre S, Franco R: Direct involvement of sigma-1 receptors in the dopamine D1 receptor-mediated effects of cocaine. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18676-81. doi: 10.1073/pnas.1008911107. Epub 2010 Oct 18. [PubMed:20956312]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
substrate for metabolism
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Brzezinski MR, Spink BJ, Dean RA, Berkman CE, Cashman JR, Bosron WF: Human liver carboxylesterase hCE-1: binding specificity for cocaine, heroin, and their metabolites and analogs. Drug Metab Dispos. 1997 Sep;25(9):1089-96. [PubMed:9311626]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Ladona MG, Gonzalez ML, Rane A, Peter RM, de la Torre R: Cocaine metabolism in human fetal and adult liver microsomes is related to cytochrome P450 3A expression. Life Sci. 2000 Dec 15;68(4):431-43. [PubMed:11205892]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Shen H, He MM, Liu H, Wrighton SA, Wang L, Guo B, Li C: Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. Drug Metab Dispos. 2007 Aug;35(8):1292-300. doi: 10.1124/dmd.107.015354. Epub 2007 Apr 30. [PubMed:17470523]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Chen Y, Goldstein JA: The transcriptional regulation of the human CYP2C genes. Curr Drug Metab. 2009 Jul;10(6):567-78. Epub 2009 Jul 15. [PubMed:19702536]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Grundemann D, Koster S, Kiefer N, Breidert T, Engelhardt M, Spitzenberger F, Obermuller N, Schomig E: Transport of monoamine transmitters by the organic cation transporter type 2, OCT2. J Biol Chem. 1998 Nov 20;273(47):30915-20. [PubMed:9812985]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:53