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 3101.12 65.88 837 5211 62571 46617443
Toxicity to various agents 1657.55 65.88 707 5341 211059 46468955
Completed suicide 1132.79 65.88 487 5561 145433 46534581
Cardio-respiratory arrest 637.97 65.88 252 5796 59617 46620397
Respiratory arrest 579.52 65.88 202 5846 33614 46646400
Cardiac arrest 485.67 65.88 235 5813 90164 46589850
Death 318.72 65.88 295 5753 335253 46344761
Intentional product misuse 290.47 65.88 135 5913 46993 46633021
Substance abuse 252.10 65.88 66 5982 4101 46675913
Poisoning 221.50 65.88 79 5969 13915 46666099
Overdose 195.57 65.88 136 5912 101843 46578171
Drug dependence 125.41 65.88 58 5990 19843 46660171
Intentional overdose 102.28 65.88 77 5971 64867 46615147
Accidental overdose 100.62 65.88 50 5998 20016 46659998
Poisoning deliberate 93.18 65.88 36 6012 7890 46672124
Exposure via ingestion 92.38 65.88 29 6019 3438 46676576
Incorrect route of product administration 88.63 65.88 43 6005 16340 46663674
Drug screen positive 73.15 65.88 25 6023 3866 46676148

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 6134.88 41.23 1935 10111 80137 29860295
Toxicity to various agents 2754.04 41.23 1347 10699 175836 29764596
Respiratory arrest 867.70 41.23 354 11692 28904 29911528
Completed suicide 811.64 41.23 500 11546 98992 29841440
Intentional product misuse 716.40 41.23 325 11721 34342 29906090
Cardio-respiratory arrest 646.22 41.23 356 11690 56950 29883482
Cardiac arrest 584.22 41.23 397 11649 92453 29847979
Poisoning 501.58 41.23 184 11862 11198 29929234
Substance abuse 409.74 41.23 140 11906 6900 29933532
Overdose 356.05 41.23 284 11762 84053 29856379
Drug dependence 350.65 41.23 171 11875 21124 29919308
Asphyxia 196.25 41.23 76 11970 5349 29935083
Death 194.13 41.23 435 11611 356848 29583584
Incorrect route of product administration 139.93 41.23 75 11971 11240 29929192
Coma 136.52 41.23 120 11926 40329 29900103
Alcohol abuse 115.85 41.23 52 11994 5301 29935131
Drug abuser 112.27 41.23 48 11998 4353 29936079
Diarrhoea 104.47 41.23 8 12038 334095 29606337
Intentional overdose 103.32 41.23 104 11942 41377 29899055
Drug screen positive 102.40 41.23 45 12001 4362 29936070
Drug ineffective 91.60 41.23 14 12032 340373 29600059
Respiratory depression 83.42 41.23 54 11992 11449 29928983
Toxicologic test abnormal 81.59 41.23 23 12023 590 29939842
Poisoning deliberate 81.10 41.23 42 12004 5862 29934570
Pulmonary oedema 79.29 41.23 93 11953 43882 29896550
Fatigue 76.04 41.23 18 12028 320655 29619777
Miosis 75.53 41.23 44 12002 7732 29932700
Pyrexia 72.89 41.23 15 12031 294474 29645958
Postmortem blood drug level abnormal 71.96 41.23 17 12029 210 29940222
Pneumonia 71.36 41.23 23 12023 334283 29606149
Exposure via ingestion 65.01 41.23 28 12018 2583 29937849
Cluster headache 64.78 41.23 19 12027 563 29939869
Accidental death 64.23 41.23 26 12020 2053 29938379
Depressed level of consciousness 64.22 41.23 78 11968 38144 29902288
Accidental overdose 63.14 41.23 55 11991 18220 29922212
Dizziness 62.72 41.23 4 12042 194905 29745527
Anaemia 59.53 41.23 7 12039 207985 29732447
Rash 58.71 41.23 5 12041 191884 29748548
Agitation 58.35 41.23 89 11957 53984 29886448
Nausea 55.70 41.23 25 12021 296932 29643500
Unresponsive to stimuli 54.60 41.23 60 11986 26359 29914073
Drug use disorder 53.10 41.23 26 12020 3222 29937210
Intentional product use issue 51.13 41.23 68 11978 36372 29904060
Dyspnoea 49.81 41.23 37 12009 333258 29607174
Suicide attempt 46.23 41.23 65 11981 36632 29903800
Drug diversion 44.72 41.23 16 12030 900 29939532
Sepsis 44.25 41.23 4 12042 146391 29794041

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
MeSH PA D000779 Anesthetics, Local
MeSH PA D002317 Cardiovascular Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D015259 Dopamine Agents
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
CHEBI has role CHEBI:35337 analeptic drug
CHEBI has role CHEBI:35524 sympathomimetic
CHEBI has role CHEBI:35640 adrenergic uptake inhibitors
CHEBI has role CHEBI:35703 xenobiotic
CHEBI has role CHEBI:36333 local anesthetics
CHEBI has role CHEBI:38633 sodium channel blockers
CHEBI has role CHEBI:50949 serotonin reuptake inhibitor
CHEBI has role CHEBI:51039 dopamine reuptake inhibitors
CHEBI has role CHEBI:75771 mus musculus metabolite
CHEBI has role CHEBI:76924 plant metabolites
CHEBI has role CHEBI:78298 environmental contaminants
CHEBI has role CHEBI:77746 h. sapiens metabolites

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)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
4% NUMBRINO CODY LABS INC N209575 Jan. 10, 2020 RX SOLUTION NULLSAL Dec. 14, 2022 NEW CHEMICAL ENTITY
4% GOPRELTO GENUS LIFESCIENCES N209963 Dec. 14, 2017 RX SOLUTION NULLSAL Dec. 14, 2022 NEW CHEMICAL ENTITY
4% NUMBRINO CODY LABS INC N209575 Jan. 10, 2020 RX SOLUTION NULLSAL Jan. 10, 2023 NEW PRODUCT

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
4019690 VUID
N0000147782 NUI
D00110 KEGG_DRUG
53-21-4 SECONDARY_CAS_RN
4017521 VANDF
4019690 VANDF
C0009170 UMLSCUI
CHEBI:27958 CHEBI
COC PDB_CHEM_ID
CHEMBL120901 ChEMBL_ID
CHEMBL370805 ChEMBL_ID
CHEMBL529437 ChEMBL_ID
DB00907 DRUGBANK_ID
D003042 MESH_DESCRIPTOR_UI
446220 PUBCHEM_CID
2286 IUPHAR_LIGAND_ID
I5Y540LHVR UNII
2653 RXNORM
437 MMSL
4488 MMSL
d03878 MMSL
001369 NDDF
001370 NDDF
14816004 SNOMEDCT_US
387085005 SNOMEDCT_US
74273006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
NUMBRINO HUMAN PRESCRIPTION DRUG LABEL 1 0527-1961 SOLUTION 40 mg NULLSAL NDA 30 sections
cocaine hydrochloride nasal HUMAN PRESCRIPTION DRUG LABEL 1 0527-1971 SOLUTION 40 mg TOPICAL NDA AUTHORIZED GENERIC 30 sections
GOPRELTO HUMAN PRESCRIPTION DRUG LABEL 1 64950-359 SOLUTION 40 mg NULLSAL NDA 32 sections
cocaine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 64950-362 SOLUTION 40 mg NULLSAL NDA AUTHORIZED GENERIC 32 sections