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], [2], [3]

• Therapeutic Class: Anesthetics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 303.35
  Topological Polar Surface Area (xlogp); 2.3
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
  Bioavailability: 57% of drug becomes completely available to its intended biological destination(s) [5]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 32 mL/min/kg [6]
  Elimination: 1% of drug is excreted from urine in the unchanged form [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1 hours [6]
  Metabolism: The drug is metabolized via the hepatic [7]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 4.95 micromolar/kg/day [8]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.12% [6]
  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 [6]
  Water Solubility: The ability of drug to dissolve in water is measured as 1.6 mg/mL [4]
• 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

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	[9]
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[9]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[9]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[10]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[12]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Substrate	[13]
Butyrylcholine esterase (BCHE)	DEIHSMD	CHLE_HUMAN	Substrate	[14]

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

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]	[61]
Posaconazole	DMUL5EW	Moderate	Decreased metabolism of Cocaine caused by Posaconazole mediated inhibition of CYP450 enzyme.	Aspergillosis [1F20]	[62]
Dalfopristin	DM4LTKV	Moderate	Decreased metabolism of Cocaine caused by Dalfopristin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[63]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Cocaine caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[64]
Nefazodone	DM4ZS8M	Moderate	Decreased metabolism of Cocaine caused by Nefazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[65]
Selegiline	DM6034S	Major	Increased risk of hyperpyrexia by the combination of Cocaine and Selegiline.	Depression [6A70-6A7Z]	[61]
Isocarboxazid	DMAF1NB	Major	Increased risk of hyperpyrexia by the combination of Cocaine and Isocarboxazid.	Depression [6A70-6A7Z]	[61]
Itraconazole	DMCR1MV	Moderate	Decreased metabolism of Cocaine caused by Itraconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[66]
Procarbazine	DMIK367	Major	Increased risk of hyperpyrexia by the combination of Cocaine and Procarbazine.	Hodgkin lymphoma [2B30]	[61]
Fosamprenavir	DM4W9B3	Moderate	Decreased metabolism of Cocaine caused by Fosamprenavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[67]
Saquinavir	DMG814N	Moderate	Decreased metabolism of Cocaine caused by Saquinavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[68]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Cocaine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[69]
Ozanimod	DMT6AM2	Major	Additive hypertensive effects by the combination of Cocaine and Ozanimod.	Multiple sclerosis [8A40]	[61]
Bupropion	DM5PCS7	Major	Increased risk of lowers seizure threshold by the combination of Cocaine and Bupropion.	Nicotine use disorder [6C4A]	[70]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Cocaine caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[71]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Cocaine caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[65]
Temsirolimus	DMS104F	Moderate	Increased plasma concentrations of Cocaine and Temsirolimus due to competitive inhibition of the same metabolic pathway.	Renal cell carcinoma [2C90]	[72]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Cocaine caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[73]

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