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Identification
- Summary
Cocaine is an ester local anesthetic used during diagnostic procedures and surgeries in or through the nasal cavities.
- Brand Names
- Goprelto, Numbrino
- Generic Name
- Cocaine
- DrugBank Accession Number
- DB00907
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Illicit
- Structure
Structure for Cocaine (DB00907)
- Weight
- Average: 303.3529
Monoisotopic: 303.147058165 - Chemical Formula
- C17H21NO4
- 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
- Cocaine
- 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
Pharmacology
- Indication
For the introduction of local (topical) anesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities.
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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.
Target Actions Organism ASodium-dependent dopamine transporter inhibitorHumans ASodium-dependent noradrenaline transporter inhibitorHumans ASodium channel protein inhibitorHumans ASodium-dependent serotonin transporter inhibitorHumans UMuscarinic acetylcholine receptor M1 antagonistHumans UMuscarinic acetylcholine receptor M2 antagonistHumans USigma non-opioid intracellular receptor 1 agonistHumans ULiver carboxylesterase 1 binderHumans - 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.
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- Route of elimination
Not Available
- Half-life
1 hour
- Clearance
Not Available
- Adverse Effects
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Intense agitation, convulsions, hypertension, rhythm disturbance, coronary insufficiency, hyperthermia, rhabdomyolysis, and renal impairment. Oral mouse LD50 = 96 mg/kg
- Pathways
Pathway Category Cocaine Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Cocaine can be increased when it is combined with Abametapir. Abemaciclib The risk or severity of methemoglobinemia can be increased when Abemaciclib is combined with Cocaine. Abiraterone The risk or severity of methemoglobinemia can be increased when Abiraterone is combined with Cocaine. Acebutolol The metabolism of Acebutolol can be decreased when combined with Cocaine. Acetaminophen The risk or severity of methemoglobinemia can be increased when Acetaminophen is combined with Cocaine. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Cocaine hydrochloride XH8T8T6WZH 53-21-4 PIQVDUKEQYOJNR-VZXSFKIWSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cocaine Hydrochloride Solution 40 mg/1mL Topical Lannett Company, Inc. 2008-12-01 2020-08-31 US 
Cocaine Hydrochloride Solution 100 mg/1mL Topical Lannett Company, Inc. 2008-12-01 2020-08-31 US Cocaine Hydrochloride Top Sol 40mg/ml Liquid 40 mg / mL Topical Sandoz Canada Incorporated 1992-12-31 2019-08-01 Canada 
Cocaine Hydrochloride Topical Sol 10% Liquid 100 mg / mL Topical Sandoz Canada Incorporated 1992-12-31 2019-08-01 Canada Goprelto Solution 40 mg/1mL Nasal Genus Lifesciences Inc. 2018-01-08 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cocaine Hydrochloride Solution 40 mg/1mL Nasal Genus Lifesciences Inc. 2018-06-04 Not applicable US Cocaine Hydrochloride Solution 40 mg/1mL Nasal LXO US Inc. 2024-01-29 Not applicable US Cocaine Hydrochloride Nasal Solution 40 mg/1mL Topical OMNIVIUM PHARMACEUTICALS LLC. 2023-10-15 Not applicable US Cocaine Hydrochloride Nasal Solution 40 mg/1mL Topical Lannett Company, Inc. 2020-01-10 2024-08-31 US PMS-cocaine Hydrochloride Topical Sol 10% Liquid 100 mg / mL Topical Pharmascience Inc 1995-12-31 Not applicable Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Cocaine Hydrochloride Cocaine hydrochloride (40 mg/1mL) Solution Topical Lannett Company, Inc. 2008-12-01 2020-08-31 US Cocaine Hydrochloride Cocaine hydrochloride (100 mg/1mL) Solution Topical Lannett Company, Inc. 2008-12-01 2020-08-31 US
Categories
- ATC Codes
- S01HA01 — CocaineS02DA02 — CocaineN01BC01 — CocaineR02AD03 — Cocaine
- Drug Categories
- Agents producing tachycardia
- Agents that reduce seizure threshold
- Alkaloids
- Analgesics and Anesthetics
- Anesthetics
- Anesthetics, Local
- Anticholinergic Agents
- Aza Compounds
- Azabicyclo Compounds
- Cardiovascular Agents
- Central Nervous System Agents
- Central Nervous System Stimulants
- Cholinesterase substrates
- Cocaine, antagonists & inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dopamine Agents
- Dopamine Uptake Inhibitors
- Esters of Benzoic Acid
- Highest Risk QTc-Prolonging Agents
- Local Anesthetics (Ester)
- Membrane Transport Modulators
- Muscarinic Antagonists
- Nervous System
- Neurotransmitter Agents
- Neurotransmitter Uptake Inhibitors
- OCT2 Inhibitors
- Ophthalmologicals
- QTc Prolonging Agents
- Sensory Organs
- Sensory System Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Throat Preparations
- Tropanes
- Vasoconstrictor Agents
- Chemical TaxonomyProvided by Classyfire
- 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
- Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzoate ester / Benzoyl / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Dicarboxylic 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)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- I5Y540LHVR
- CAS number
- 50-36-2
- 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
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
- Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT: Cocaine in herbal tea. JAMA. 1986 Jan 3;255(1):40. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- FDA Approved Products: Numbrino (cocaine hydrochloride) nasal solution [Link]
- FDA Approved Products: Goprelto (cocaine hydrochloride) nasal solution [Link]
- DailyMed: Cocaine hydrochloride solution [Link]
- External Links
- Human Metabolome Database
- HMDB0015043
- KEGG Drug
- D00110
- KEGG Compound
- C01416
- PubChem Compound
- 446220
- PubChem Substance
- 46506326
- ChemSpider
- 10194104
- BindingDB
- 22418
- 2653
- ChEBI
- 27958
- ChEMBL
- CHEMBL370805
- ZINC
- ZINC000003875336
- Therapeutic Targets Database
- DAP000834
- PharmGKB
- PA449072
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- COC
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Cocaine
- PDB Entries
- 1i7z / 1q72 / 2ajv / 2pgz / 4xp4 / 4xpb / 8de3 / 9eo4
- MSDS
- Download (104 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Treatment Age - Related Macular Degeneration (AMD) 1 somestatus stop reason just information to hide 4 Completed Other Chronic Sinusitis 1 somestatus stop reason just information to hide 4 Completed Prevention Epistaxis 1 somestatus stop reason just information to hide 4 Not Yet Recruiting Prevention ENT Disorder 1 somestatus stop reason just information to hide 4 Unknown Status Treatment Alcohol Dependency / Dependence, Cocaine 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Cody Laboratories Inc.
- Lannett Co. Inc.
- Mallinckrodt Inc.
- Roxane Labs
- Dosage Forms
Form Route Strength Solution Topical 100 mg/1mL Solution Topical 40 mg/1mL Liquid Topical 40 mg / mL Liquid Topical 100 mg / mL Solution Nasal 40 mg/1mL - Prices
Unit description Cost Unit Cocaine hydrochloride powder 68.44USD g Cocaine 10% solution 10.68USD ml Cocaine 4% solution 6.22USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9867815 No 2018-01-16 2037-02-07 US US10016407 No 2018-07-10 2037-02-07 US US10149843 No 2018-12-11 2037-02-07 US US10231961 No 2019-03-19 2037-02-07 US US10413505 No 2019-09-17 2037-02-07 US US10420760 No 2019-09-24 2037-02-07 US US10857095 No 2020-12-08 2037-02-07 US US10894012 No 2021-01-19 2037-02-07 US US10933060 No 2021-03-02 2037-02-07 US US10973811 No 2021-04-13 2037-02-07 US US10987347 No 2021-04-27 2037-02-07 US US11040032 No 2021-06-22 2037-02-07 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 98 °C PhysProp water solubility 1800 mg/L (at 22 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 2.30 HANSCH,C ET AL. (1995) logS -2.23 ADME Research, USCD pKa 8.61 (at 15 °C) MERCK INDEX (1996) - Predicted Properties
Property Value Source Water Solubility 5.03 mg/mL ALOGPS logP 1.97 ALOGPS logP 2.28 Chemaxon logS -1.8 ALOGPS pKa (Strongest Basic) 8.85 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 55.84 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 81.16 m3·mol-1 Chemaxon Polarizability 32.02 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8644 Blood Brain Barrier + 0.8805 Caco-2 permeable + 0.7654 P-glycoprotein substrate Substrate 0.5 P-glycoprotein inhibitor I Inhibitor 0.8168 P-glycoprotein inhibitor II Non-inhibitor 0.893 Renal organic cation transporter Inhibitor 0.6182 CYP450 2C9 substrate Non-substrate 0.7897 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.6856 CYP450 1A2 substrate Non-inhibitor 0.8627 CYP450 2C9 inhibitor Non-inhibitor 0.9341 CYP450 2D6 inhibitor Non-inhibitor 0.5614 CYP450 2C19 inhibitor Non-inhibitor 0.9383 CYP450 3A4 inhibitor Non-inhibitor 0.9237 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9408 Ames test Non AMES toxic 0.7437 Carcinogenicity Non-carcinogens 0.9585 Biodegradation Not ready biodegradable 0.5319 Rat acute toxicity 2.6387 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8463 hERG inhibition (predictor II) Non-inhibitor 0.8042
Spectra
- Mass Spec (NIST)
- Download (2.96 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 174.4089035 predictedDarkChem Lite v0.1.0 [M-H]- 173.6360035 predictedDarkChem Lite v0.1.0 [M-H]- 170.43347 predictedDeepCCS 1.0 (2019) [M+H]+ 173.1699035 predictedDarkChem Lite v0.1.0 [M+H]+ 173.3030035 predictedDarkChem Lite v0.1.0 [M+H]+ 172.82906 predictedDeepCCS 1.0 (2019) [M+Na]+ 173.5483035 predictedDarkChem Lite v0.1.0 [M+Na]+ 173.1510035 predictedDarkChem Lite v0.1.0 [M+Na]+ 179.20958 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:8302271). Also mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (By similarity). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling (By similarity)
- Specific Function
- Amine binding
- Gene Name
- SLC6A3
- Uniprot ID
- Q01959
- Uniprot Name
- Sodium-dependent dopamine transporter
- Molecular Weight
- 68494.255 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article]
- 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. [Article]
- Verma V: Classic Studies on the Interaction of Cocaine and the Dopamine Transporter. Clin Psychopharmacol Neurosci. 2015 Dec 31;13(3):227-38. doi: 10.9758/cpn.2015.13.3.227. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (PubMed:2008212, PubMed:8125921). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921)
- Specific Function
- Actin binding
- Gene Name
- SLC6A2
- Uniprot ID
- P23975
- Uniprot Name
- Sodium-dependent noradrenaline transporter
- Molecular Weight
- 69331.42 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Siegel GJ, Agranoff BW, Albers RW et al. (1999). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott Williams.
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 (PubMed:14672992). Plays a key role in brain, probably by regulating the moment when neurotransmitters are released in neurons. Involved in sensory perception of mechanical pain: activation in somatosensory neurons induces pain without neurogenic inflammation and produces hypersensitivity to mechanical, but not thermal stimuli
- Specific Function
- Voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
Components:
References
- 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. [Article]
- Crumb WJ Jr, Clarkson CW: Characterization of cocaine-induced block of cardiac sodium channels. Biophys J. 1990 Mar;57(3):589-99. doi: 10.1016/S0006-3495(90)82574-1. [Article]
- Siegel GJ, Agranoff BW, Albers RW et al. (1999). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott Williams.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:17506858, PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity)
- Specific Function
- Actin filament binding
- Gene Name
- SLC6A4
- Uniprot ID
- P31645
- Uniprot Name
- Sodium-dependent serotonin transporter
- Molecular Weight
- 70324.165 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article]
- 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. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Siegel GJ, Agranoff BW, Albers RW et al. (1999). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott Williams.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General 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
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- CHRM1
- Uniprot ID
- P11229
- Uniprot Name
- Muscarinic acetylcholine receptor M1
- Molecular Weight
- 51420.375 Da
References
- Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General 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
- Specific Function
- Arrestin family protein binding
- Gene Name
- CHRM2
- Uniprot ID
- P08172
- Uniprot Name
- Muscarinic acetylcholine receptor M2
- Molecular Weight
- 51714.605 Da
References
- Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General 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. Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112 (By similarity)
- Specific Function
- G protein-coupled opioid receptor activity
- Gene Name
- SIGMAR1
- Uniprot ID
- Q99720
- Uniprot Name
- Sigma non-opioid intracellular receptor 1
- Molecular Weight
- 25127.52 Da
References
- 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. [Article]
- 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. [Article]
- Narayanan S, Mesangeau C, Poupaert JH, McCurdy CR: Sigma receptors and cocaine abuse. Curr Top Med Chem. 2011;11(9):1128-50. doi: 10.2174/156802611795371323. [Article]
- Yasui Y, Su TP: Potential Molecular Mechanisms on the Role of the Sigma-1 Receptor in the Action of Cocaine and Methamphetamine. J Drug Alcohol Res. 2016 Feb 20;5. doi: 10.4303/jdar/235970. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- Curator comments
- substrate for metabolism
- General Function
- Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644). Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644). Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644). Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984). Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:11015575, PubMed:16024911, PubMed:16971496, PubMed:18762277). First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:16971496, PubMed:18599737, PubMed:18762277)
- Specific Function
- Carboxylesterase activity
- Gene Name
- CES1
- Uniprot ID
- P23141
- Uniprot Name
- Liver carboxylesterase 1
- Molecular Weight
- 62520.62 Da
References
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
- Chen X, Zheng X, Zhan M, Zhou Z, Zhan CG, Zheng F: Metabolic Enzymes of Cocaine Metabolite Benzoylecgonine. ACS Chem Biol. 2016 Aug 19;11(8):2186-94. doi: 10.1021/acschembio.6b00277. Epub 2016 Jun 9. [Article]
- Flockhart Table of Drug Interactions [Link]
- FDA Approved Products: Numbrino (cocaine hydrochloride) nasal solution [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Downregulator
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- Arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- 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. [Article]
- Malaplate-Armand C, Ferrari L, Masson C, Visvikis-Siest S, Lambert H, Batt AM: Down-regulation of astroglial CYP2C, glucocorticoid receptor and constitutive androstane receptor genes in response to cocaine in human U373 MG astrocytoma cells. Toxicol Lett. 2005 Dec 15;159(3):203-11. doi: 10.1016/j.toxlet.2005.04.005. Epub 2005 Sep 26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters
- Specific Function
- Acetylcholinesterase activity
- Gene Name
- BCHE
- Uniprot ID
- P06276
- Uniprot Name
- Cholinesterase
- Molecular Weight
- 68417.575 Da
References
- Grasing K, Mathur D, DeSouza C, Newton TF, Moody DE, Sturgill M: Cocaine cardiovascular effects and pharmacokinetics after treatment with the acetylcholinesterase inhibitor donepezil. Am J Addict. 2016 Aug;25(5):392-9. doi: 10.1111/ajad.12402. Epub 2016 Jul 8. [Article]
- Schwartz HJ, Johnson D: In vitro competitive inhibition of plasma cholinesterase by cocaine: normal and variant genotypes. J Toxicol Clin Toxicol. 1996;34(1):77-81. doi: 10.3109/15563659609020237. [Article]
- FDA Approved Products: Numbrino (cocaine hydrochloride) nasal solution [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644). Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644). Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644). Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984). Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:11015575, PubMed:16024911, PubMed:16971496, PubMed:18762277). First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:16971496, PubMed:18599737, PubMed:18762277)
- Specific Function
- Carboxylesterase activity
- Gene Name
- CES1
- Uniprot ID
- P23141
- Uniprot Name
- Liver carboxylesterase 1
- Molecular Weight
- 62520.62 Da
References
- 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. [Article]
- FDA Approved Products: Numbrino (cocaine hydrochloride) nasal solution [Link]
Carriers
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
Components:
References
- Edwards DJ, Bowles SK: Protein binding of cocaine in human serum. Pharm Res. 1988 Jul;5(7):440-2. doi: 10.1023/a:1015992502509. [Article]
- Parker RB, Williams CL, Laizure SC, Lima JJ: Factors affecting serum protein binding of cocaine in humans. J Pharmacol Exp Ther. 1995 Nov;275(2):605-10. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Data suggest that cocaine is a weak inhibitor.
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- Acetylcholine transmembrane transporter activity
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:8302271). Also mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (By similarity). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling (By similarity)
- Specific Function
- Amine binding
- Gene Name
- SLC6A3
- Uniprot ID
- Q01959
- Uniprot Name
- Sodium-dependent dopamine transporter
- Molecular Weight
- 68494.255 Da
References
- 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. [Article]
- Crits-Christoph P, Newberg A, Wintering N, Ploessl K, Gibbons MB, Ring-Kurtz S, Gallop R, Present J: Dopamine transporter levels in cocaine dependent subjects. Drug Alcohol Depend. 2008 Nov 1;98(1-2):70-6. doi: 10.1016/j.drugalcdep.2008.04.014. Epub 2008 Jun 20. [Article]
- Mash DC, Pablo J, Ouyang Q, Hearn WL, Izenwasser S: Dopamine transport function is elevated in cocaine users. J Neurochem. 2002 Apr;81(2):292-300. doi: 10.1046/j.1471-4159.2002.00820.x. [Article]
Drug created at June 13, 2005 13:24 / Updated at September 15, 2024 01:12