Details of the Drug

General Information of Drug (ID: DMSOX7I)

Drug Name

Cocaine

Synonyms

Allococaine; Allopseudococaine; Badrock; Bazooka; Benzoylethylecgonine; Benzoylmethylecgonine; Bernice; Bernies; Blast; Blizzard; Blow; Burese; COC; Cabello; Candy; Carrie; Caviar; Cecil; Charlie; Cholly; Coca; Cocain; Cocaina; Cocainum; Cocktail; Coke; Cola; Corine; Crack; Eritroxilina; Erytroxylin; Flake; Flex; Freeze; Girl; Goofball; Heaven; Hell; Jam; Kokain; Kokan; Kokayeen; Lady; Leaf; Moonrocks; Neurocaine; Pseudoallococaine; Rock; Sleighride; Snort; Snow; Toke; Toot; Trails; Yeyo; Bernice [Street Name]; Blow [Street Name]; Bouncing Powder; Cecil [Street Name]; Chicken Scratch; Cocaine [BAN]; Cocaine free base; Cocaine solution; Crack cocaine; Dama blanca; Ecgonine methyl ester benzoate; Ecgonine methyl ester benzoate solution; Flake [Street Name]; Florida Snow; Foo Foo; Girl [Street Name]; Gold dust; Gold dust [Street Name]; Green gold; Happy dust; Happy dust [Street Name]; Happy powder; Happy trails; Lady [Street Name]; Methyl Benzoylecgonine; Nose candy; Prime Time; Rock [Street Name]; Sweet Stuff; Toot [Street Name]; White girl or lady; Beta-Cocain; C" Carrie; Cocaine (TN); Cocaine (USP); Cocaine-M; G-Rock; Kibbles n' Bits; L-Cocain; L-Cocaine; Pimp's drug; Snow (birds); Star-spangled powder; Ecgonine, methyl ester, benzoate (ester); Methyl 3beta-hydroxy-1alphaH,5alphaH-tropane-2beta-carboxylate benzoate (ester); Methyl 3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylate; Methyl 3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate; Methyl (3S,4R)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylate; Methyl (1S,4R,5R)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylate; (-)-Cocaine; (-)-Cocaine base; (1R,2R,3S,5S)-2-(methoxycarbonyl)tropan-3-yl benzoate; (1R,2R,3S,5S)-2-Methoxycarbonyltropan-3-yl benzoate; (R)-Cocaine; 1-Cocaine; 2-beta-Carbomethoxy-3-beta-benzoxytropane; 2-beta-Tropanecarboxylic acid, 3-beta-hydroxy-, methyl ester, benzoate (ester); 2beta-Carbomethoxy-3beta-benzoxytropane; 3-Tropanylbenzoate-2-carboxylic acid methyl ester; 3beta-Hydroxy-2beta-tropanecarboxylic acid methyl ester benzoate (ester)

Indication

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[1]
Cocaine addiction	6C45.2	Approved	[2]
------------------------------------------------------------------------------------

Therapeutic Class

Anesthetics

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

303.35

Logarithm of the Partition Coefficient (xlogp)

2.3

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Bioavailability: 57% of drug becomes completely available to its intended biological destination(s) [4]
Clearance: The drug present in the plasma can be removed from the body at the rate of 32 mL/min/kg [5]
Elimination: 1% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 1 hours [5]
Metabolism: The drug is metabolized via the hepatic []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 4.95 micromolar/kg/day [6]
Unbound Fraction: The unbound fraction of drug in plasma is 0.12% [5]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 2 L/kg [5]
Water Solubility: The ability of drug to dissolve in water is measured as 1.6 mg/mL [3]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Liver injury	Not Available	GPT	OTOXOA0Q	[7]
-----------

Chemical Identifiers

Formula: C17H21NO4
IUPAC Name: methyl (1R,2R,3S,5S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
Canonical SMILES: CN1[C@H]2CC[C@@H]1[C@H]([C@H](C2)OC(=O)C3=CC=CC=C3)C(=O)OC
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
InChIKey: ZPUCINDJVBIVPJ-LJISPDSOSA-N

Cross-matching ID

PubChem CID: 446220
ChEBI ID: CHEBI:27958
CAS Number: 50-36-2
DrugBank ID: DB00907
TTD ID: D04XPW
VARIDT ID: DR00530
INTEDE ID: DR0365

Combinatorial Drugs (CBD)

Click to Jump to the Detailed CBD Information of This Drug

Repurposed Drugs (RPD)

Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine transporter (DAT)	TTVBI8W	SC6A3_HUMAN	Inhibitor	[8]
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[8]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[8]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[11]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Substrate	[12]
Butyrylcholine esterase (BCHE)	DEIHSMD	CHLE_HUMAN	Substrate	[13]

------------------------------------------------------------------------------------

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
14-3-3 protein epsilon	OT3WQXNA	1433E_HUMAN	Gene/Protein Processing	[14]
14-3-3 protein eta	OTP8NJFJ	1433F_HUMAN	Gene/Protein Processing	[15]
5-hydroxymethyl-dUMP N-hydrolase (DNPH1)	OTEZVTI1	DNPH1_HUMAN	Gene/Protein Processing	[16]
60 kDa heat shock protein, mitochondrial (HSPD1)	OTTO1Y11	CH60_HUMAN	Gene/Protein Processing	[17]
Actin, gamma-enteric smooth muscle (ACTG2)	OTRDWUO0	ACTH_HUMAN	Gene/Protein Processing	[14]
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Gene/Protein Processing	[16]
Adropin (ENHO)	OT91QASK	ENHO_HUMAN	Gene/Protein Processing	[18]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Drug Response	[7]
Allograft inflammatory factor 1-like (AIF1L)	OTDEOB80	AIF1L_HUMAN	Gene/Protein Processing	[16]
Alpha-actinin-2 (ACTN2)	OT9FOLD7	ACTN2_HUMAN	Gene/Protein Processing	[16]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Anaesthesia

ICD Disease Classification

9A78.6

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine transporter (DAT)	DTT	SLC6A3	1.08E-03	-3.08	-1.99
Serotonin transporter (SERT)	DTT	SLC6A4	8.76E-01	7.18E-05	6.19E-04
Butyrylcholine esterase (BCHE)	DME	BCHE	9.05E-01	-6.21E-02	-6.30E-02
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	9.57E-01	9.43E-03	1.29E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.70E-01	2.98E-02	1.22E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.76E-01	1.26E-01	8.27E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Cocaine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Major	Increased risk of hyperpyrexia by the combination of Cocaine and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[19]
Posaconazole	DMUL5EW	Moderate	Decreased metabolism of Cocaine caused by Posaconazole mediated inhibition of CYP450 enzyme.	Aspergillosis [1F20]	[20]
Dalfopristin	DM4LTKV	Moderate	Decreased metabolism of Cocaine caused by Dalfopristin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[21]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Cocaine caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[22]
Nefazodone	DM4ZS8M	Moderate	Decreased metabolism of Cocaine caused by Nefazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[23]
Selegiline	DM6034S	Major	Increased risk of hyperpyrexia by the combination of Cocaine and Selegiline.	Depression [6A70-6A7Z]	[19]
Isocarboxazid	DMAF1NB	Major	Increased risk of hyperpyrexia by the combination of Cocaine and Isocarboxazid.	Depression [6A70-6A7Z]	[19]
Itraconazole	DMCR1MV	Moderate	Decreased metabolism of Cocaine caused by Itraconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[24]
Procarbazine	DMIK367	Major	Increased risk of hyperpyrexia by the combination of Cocaine and Procarbazine.	Hodgkin lymphoma [2B30]	[19]
Fosamprenavir	DM4W9B3	Moderate	Decreased metabolism of Cocaine caused by Fosamprenavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[25]
Saquinavir	DMG814N	Moderate	Decreased metabolism of Cocaine caused by Saquinavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[26]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Cocaine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[27]
Ozanimod	DMT6AM2	Major	Additive hypertensive effects by the combination of Cocaine and Ozanimod.	Multiple sclerosis [8A40]	[19]
Bupropion	DM5PCS7	Major	Increased risk of lowers seizure threshold by the combination of Cocaine and Bupropion.	Nicotine use disorder [6C4A]	[28]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Cocaine caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[29]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Cocaine caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[23]
Temsirolimus	DMS104F	Moderate	Increased plasma concentrations of Cocaine and Temsirolimus due to competitive inhibition of the same metabolic pathway.	Renal cell carcinoma [2C90]	[30]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Cocaine caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[31]
-----------


⏷ Show the Full List of 18 DDI Information of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2286).
2	Cocaine FDA Label
3	BDDCS applied to over 900 drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
8	Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav. 2009 Jul;93(1):75-81.
9	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
10	Neuronal cytochrome P450IID1 (debrisoquine/sparteine-type): potent inhibition of activity by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. Mol Pharmacol. 1991 Jul;40(1):63-8.
11	Regenerative changes in hepatic morphology and enhanced expression of CYP2B10 and CYP3A during daily administration of cocaine. Hepatology. 1996 Mar;23(3):515-23.
12	Drug Interactions Flockhart Table
13	An albumin-butyrylcholinesterase for cocaine toxicity and addiction: catalytic and pharmacokinetic properties. Chem Biol Interact. 2008 Sep 25;175(1-3):83-7.
14	Gene expression profiling reveals distinct cocaine-responsive genes in human fetal CNS cell types. J Addict Med. 2009 Dec;3(4):218-26. doi: 10.1097/ADM.0b013e318199d863.
15	Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
16	Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
17	Proteomic analysis of the nucleus accumbens of rats with different vulnerability to cocaine addiction. Neuropharmacology. 2009 Jul;57(1):41-8. doi: 10.1016/j.neuropharm.2009.04.005. Epub 2009 Apr 22.
18	Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
19	Product Information. Cocaine Hydrochloride Nasal (cocaine nasal). Genus Lifesciences Inc., Allentown, PA.
20	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
21	Product Information. Synercid (dalfopristin-quinupristin) Rhone-Poulenc Rorer, Collegeville, PA.
22	Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83. [PMID: 9834039]
23	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
24	Auclair B, Berning SE, Huitt GA, Peloquin CP "Potential interaction between itraconazole and clarithromycin." Pharmacotherapy 19 (1999): 1439-44. [PMID: 10600094]
25	Product Information. Agenerase (amprenavir). Glaxo Wellcome, Research Triangle Pk, NC.
26	Cerner Multum, Inc. "Australian Product Information.".
27	Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
28	Sheehan DV, Welch JB, Fishman SM "A case of bupropion-induced seizure." J Nerv Ment Dis 174 (1986): 496-8. [PMID: 3090199]
29	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
30	Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
31	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.