cocaine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
local anaesthetics 723 50-36-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • cocaine
  • cocain
  • benzoylmethylecgonine
  • cocaine hydrochloride
  • cocaine HCl
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.
  • Molecular weight: 303.36
  • Formula: C17H21NO4
  • CLOGP: 2.57
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 0
  • TPSA: 55.84
  • ALOGS: -1.78
  • ROTB: 5

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 1.60 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 1 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 4.95 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 57 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 2 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 32 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.12 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.76 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Jan. 1, 1860 YEAR INTRODUCED

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug abuse 3169.12 163.65 588 1122 11438 2344937
Toxicity to various agents 2216.83 163.65 522 1188 32232 2324143
Completed suicide 1625.83 163.65 377 1333 20657 2335718
Cardio-respiratory arrest 841.16 163.65 191 1519 8955 2347420
Respiratory arrest 581.92 163.65 132 1578 6046 2350329
Death 579.08 163.65 235 1475 81233 2275142
Cardiac arrest 573.24 163.65 155 1555 14775 2341600
Intentional product misuse 393.37 163.65 105 1605 9384 2346991
Poisoning 317.74 163.65 70 1640 2750 2353625
Overdose 268.97 163.65 93 1617 19814 2336561
Substance abuse 264.30 163.65 46 1664 503 2355872

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug abuse 6710.20 134.60 1330 1751 12359 1731341
Toxicity to various agents 3625.47 134.60 939 2142 28202 1715498
Completed suicide 1363.90 134.60 393 2688 15919 1727781
Respiratory arrest 1152.31 134.60 279 2802 5560 1738140
Cardio-respiratory arrest 1094.64 134.60 294 2787 8999 1734701
Intentional product misuse 1014.55 134.60 264 2817 7094 1736606
Cardiac arrest 976.16 134.60 303 2778 15627 1728073
Poisoning 723.80 134.60 164 2917 2368 1741332
Death 660.80 134.60 371 2710 87072 1656628
Substance abuse 483.26 134.60 100 2981 903 1742797
Overdose 457.84 134.60 175 2906 16526 1727174
Drug dependence 392.08 134.60 106 2975 3221 1740479
Alcohol abuse 221.26 134.60 48 3033 549 1743151
Coma 172.81 134.60 69 3012 7193 1736507
Intentional overdose 158.94 134.60 66 3015 7604 1736096
Drug abuser 155.35 134.60 43 3038 1414 1742286
Incorrect route of product administration 153.28 134.60 52 3029 3413 1740287

Pharmacologic Action:

SourceCodeDescription
ATC N01BC01 NERVOUS SYSTEM
ANESTHETICS
ANESTHETICS, LOCAL
Esters of benzoic acid
ATC R02AD03 RESPIRATORY SYSTEM
THROAT PREPARATIONS
THROAT PREPARATIONS
Anesthetics, local
ATC S01HA01 SENSORY ORGANS
OPHTHALMOLOGICALS
LOCAL ANESTHETICS
Local anesthetics
ATC S02DA02 SENSORY ORGANS
OTOLOGICALS
OTHER OTOLOGICALS
Analgesics and anesthetics
MeSH PA D000777 Anesthetics
CHEBI has role CHEBI:35640 adrenergic uptake inhibitor
CHEBI has role CHEBI:51039 dopamine uptake inhibitor
CHEBI has role CHEBI:50949 serotonin uptake inhibitor
CHEBI has role CHEBI:50514 vasoconstrictor agent
CHEBI has role CHEBI:36333 local anaesthetic
CHEBI has role CHEBI:35337 central nervous system stimulant
CHEBI has role CHEBI:35524 sympathomimetic agent
MeSH PA D000779 Anesthetics, Local
MeSH PA D002317 Cardiovascular Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D015259 Dopamine Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D018765 Dopamine Uptake Inhibitors
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D014179 Neurotransmitter Uptake Inhibitors
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018689 Sensory System Agents
MeSH PA D014662 Vasoconstrictor Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Local anesthesia indication 386761002
Conduction disorder of the heart contraindication 44808001
Epilepsy contraindication 84757009 DOID:1826
Thyrotoxicosis contraindication 90739004 DOID:7997
Disorder of mucous membrane contraindication 95351003
Acute disease of cardiovascular system contraindication 128487001
Breastfeeding (mother) contraindication 413712001
Hypertensive urgency contraindication 443482000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.27 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NASAL 10016407 Feb. 7, 2037 METHOD OF ADMINISTERING A LOCAL ANESTHETIC PRIOR TO PERFORMING A DIAGNOSTIC OR SURGICAL PROCEDURE ON A SUBJECT WITH HEPATIC OR RENAL IMPAIRMENT
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NASAL 10149843 Feb. 7, 2037 METHOD FOR THE INDUCTION OF LOCAL ANESTHESIA PRIOR TO PERFORMING A PROCEDURE ON, THROUGH, OR ADJACENT TO THE MUCOUS MEMBRANES
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NASAL 10149843 Feb. 7, 2037 METHOD OF ADMINISTERING A LOCAL ANESTHETIC TO THE MUCOUS MEMBRANES
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NASAL 10413505 Feb. 7, 2037 METHOD OF ADMINISTERING A LOCAL ANESTHETIC TO THE MUCOUS MEMBRANES
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NASAL 10420760 Feb. 7, 2037 METHOD FOR THE INDUCTION OF LOCAL ANESTHESIA PRIOR TO PERFORMING A PROCEDURE ON, THROUGH, OR ADJACENT TO THE MUCOUS MEMBRANES
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NASAL 9867815 Feb. 7, 2037 METHOD OF ADMINISTERING A LOCAL ANESTHETIC TO THE MUCOUS MEMBRANES IN GERIATRIC PATIENTS
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NASAL 9867815 Feb. 7, 2037 METHOD OF ADMINISTERING A LOCAL ANESTHETIC TO THE MUCOUS MEMBRANES IN PATIENTS WITH HEPATIC IMPAIRMENT
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NASAL 9867815 Feb. 7, 2037 METHOD OF ADMINISTERING A LOCAL ANESTHETIC TO THE MUCOUS MEMBRANES IN PATIENTS WITH RENAL IMPAIRMENT

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NASAL Dec. 14, 2022 NEW CHEMICAL ENTITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Sodium-dependent dopamine transporter Transporter INHIBITOR UNKNOWN IUPHAR
Sodium channel alpha subunits; brain (Types I, II, III) Ion channel IC50 4.31 CHEMBL
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 5.05 CHEMBL
Sodium-dependent noradrenaline transporter Transporter Ki 5.57 WOMBAT-PK
Sodium-dependent serotonin transporter Transporter Ki 6.92 WOMBAT-PK
Cocaine- and amphetamine-regulated transcript protein Transcription factor WOMBAT-PK
Sodium- and chloride-dependent GABA transporter 1 Transporter IC50 5.50 WOMBAT-PK
5-hydroxytryptamine receptor 3A Ion channel Ki 5.71 WOMBAT-PK
Kappa-type opioid receptor GPCR IC50 5.10 WOMBAT-PK
Histamine H1 receptor GPCR Ki 5.67 WOMBAT-PK
Alpha-1A adrenergic receptor GPCR Ki 5.68 WOMBAT-PK
Sodium channel protein type 11 subunit alpha Ion channel WOMBAT-PK
5-hydroxytryptamine receptor 1B GPCR Ki 5.47 WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.14 WOMBAT-PK
Serotonin 3 receptor (5HT3) Ion channel ANTAGONIST Ki 4.80 IUPHAR
Sodium channel protein type 5 subunit alpha Ion channel WOMBAT-PK
Transporter Transporter Ki 5.50 CHEMBL
Dopamine transporter Unclassified IC50 7.19 CHEMBL
Transporter Transporter Ki 6.97 CHEMBL
Sodium-dependent dopamine transporter Transporter Ki 7.49 CHEMBL
Muscarinic acetylcholine receptor M1 GPCR Ki 4.21 CHEMBL
Dopamine transporter Unclassified IC50 7.02 CHEMBL
Sodium-dependent serotonin transporter Transporter Ki 7.35 CHEMBL

External reference:

IDSource
D003042 MESH_DESCRIPTOR_UI
4019690 VUID
N0000147782 NUI
C0009170 UMLSCUI
D00110 KEGG_DRUG
14816004 SNOMEDCT_US
4019690 VANDF
001369 NDDF
2653 RXNORM
387085005 SNOMEDCT_US
d03878 MMSL
CHEBI:27958 CHEBI
CHEMBL120901 ChEMBL_ID
CHEMBL370805 ChEMBL_ID
DB00907 DRUGBANK_ID
CHEMBL529437 ChEMBL_ID
I5Y540LHVR UNII
COC PDB_CHEM_ID
53-21-4 SECONDARY_CAS_RN
2286 IUPHAR_LIGAND_ID
446220 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Cocaine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0527-1728 SOLUTION 40 mg TOPICAL UNAPPROVED DRUG OTHER 12 sections
Cocaine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0527-1729 SOLUTION 100 mg TOPICAL UNAPPROVED DRUG OTHER 12 sections
NUMBRINO HUMAN PRESCRIPTION DRUG LABEL 1 0527-1961 SOLUTION 40 mg TOPICAL NDA 18 sections
GOPRELTO HUMAN PRESCRIPTION DRUG LABEL 1 64950-359 SOLUTION 40 mg NASAL NDA 19 sections
cocaine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 64950-362 SOLUTION 40 mg NASAL NDA AUTHORIZED GENERIC 19 sections