Cocaine

Cocaine is a tropane 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. Cocaine binds to the dopamine, serotonin, and norepinephrine transport proteins and inhibits the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. This leads to an accumulation of the respective neurotransmitters in the synaptic cleft and may result in increased postsynaptic receptor activation. The mechanism of action through which cocaine exerts its local anesthetic effects is by binding to and blocking the voltage-gated sodium channels in the neuronal cell membrane. By stabilizing neuronal membranes, cocaine inhibits the initiation and conduction of nerve impulses and produces a reversible loss of sensation. (from PubChem) Cocaine is hydrolized by BChE and very efficiently by mutants of BChE

General

Type : Natural, Not A\/B H target, Drug, Alkaloid, Benzoate

Chemical_Nomenclature : 2beta-carbomethoxy-3beta-benzoyloxytropane hydrochloride

Canonical SMILES : CN1C2CCC1C(C(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

Other name(s) : (-)-Cocaine  ||  3-beta-Hydroxy-, Methyl Ester, Benzoate  ||  Methylbenzoylepgonine  ||  Cocaine Free Base  ||  Benzoylmethylecgonine  ||  Crack  ||  L-Cocain  ||  beta-Cocain  ||  D-cocaine


MW : 339.82

Formula : C17H21NO4.HCl

CAS_number : 53-21-4

PubChem : 446220

UniChem : ZPUCINDJVBIVPJ-LJISPDSOSA-N

IUPHAR : 2286

Wikipedia : Cocaine

Target

Families : Cocaine ligand of proteins in family
BCHE

Structure :
3O9M

Protein :
human-BCHE

References (15)

Title : Kinetic characterization of a cocaine hydrolase engineered from mouse butyrylcholinesterase - Chen_2015_Biochem.J_466_243
Author(s) : Chen X , Huang X , Geng L , Xue L , Hou S , Zheng X , Brimijoin S , Zheng F , Zhan CG
Ref : Biochemical Journal , 466 :243 , 2015
Abstract :
PubMedSearch : Chen_2015_Biochem.J_466_243
PubMedID: 25486543
Gene_locus related to this paper: human-BCHE

Title : Reward and Toxicity of Cocaine Metabolites Generated by Cocaine Hydrolase - Murthy_2015_Cell.Mol.Neurobiol_35_819
Author(s) : Murthy V , Geng L , Gao Y , Zhang B , Miller JD , Reyes S , Brimijoin S
Ref : Cellular Molecular Neurobiology , 35 :819 , 2015
Abstract :
PubMedSearch : Murthy_2015_Cell.Mol.Neurobiol_35_819
PubMedID: 25814464

Title : A highly efficient cocaine-detoxifying enzyme obtained by computational design - Zheng_2014_Nat.Commun_5_3457
Author(s) : Zheng F , Xue L , Hou S , Liu J , Zhan M , Yang W , Zhan CG
Ref : Nat Commun , 5 :3457 , 2014
Abstract :
PubMedSearch : Zheng_2014_Nat.Commun_5_3457
PubMedID: 24643289
Gene_locus related to this paper: human-BCHE

Title : Amino-acid mutations to extend the biological half-life of a therapeutically valuable mutant of human butyrylcholinesterase - Fang_2014_Chem.Biol.Interact_214C_18
Author(s) : Fang L , Hou S , Xue L , Zheng F , Zhan CG
Ref : Chemico-Biological Interactions , 214C :18 , 2014
Abstract :
PubMedSearch : Fang_2014_Chem.Biol.Interact_214C_18
PubMedID: 24582612
Gene_locus related to this paper: human-BCHE

Title : Rational design, preparation, and characterization of a therapeutic enzyme mutant with improved stability and function for cocaine detoxification - Fang_2014_ACS.Chem.Biol_9_1764
Author(s) : Fang L , Chow KM , Hou S , Xue L , Chen X , Rodgers DW , Zheng F , Zhan CG
Ref : ACS Chemical Biology , 9 :1764 , 2014
Abstract :
PubMedSearch : Fang_2014_ACS.Chem.Biol_9_1764
PubMedID: 24919140
Gene_locus related to this paper: rhosm-cocE

Title : Preclinical studies on neurobehavioral and neuromuscular effects of cocaine hydrolase gene therapy in mice - Murthy_2014_J.Mol.Neurosci_53_409
Author(s) : Murthy V , Gao Y , Geng L , LeBrasseur NK , White TA , Brimijoin S
Ref : Journal of Molecular Neuroscience , 53 :409 , 2014
Abstract :
PubMedSearch : Murthy_2014_J.Mol.Neurosci_53_409
PubMedID: 24085526

Title : The future potential for cocaine vaccines - Orson_2014_Expert.Opin.Biol.Ther_14_1271
Author(s) : Orson FM , Wang R , Brimijoin S , Kinsey BM , Singh RA , Ramakrishnan M , Wang HY , Kosten TR
Ref : Expert Opin Biol Ther , 14 :1271 , 2014
Abstract :
PubMedSearch : Orson_2014_Expert.Opin.Biol.Ther_14_1271
PubMedID: 24835496

Title : Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity - Larrimore_2013_Chem.Biol.Interact_203_217
Author(s) : Larrimore KE , Barcus M , Kannan L , Gao Y , Zhan CG , Brimijoin S , Mor TS
Ref : Chemico-Biological Interactions , 203 :217 , 2013
Abstract :
PubMedSearch : Larrimore_2013_Chem.Biol.Interact_203_217
PubMedID: 23000451

Title : Catalytic activities of a cocaine hydrolase engineered from human butyrylcholinesterase against (+)- and (-)-cocaine - Xue_2013_Chem.Biol.Interact_203_57
Author(s) : Xue L , Hou S , Yang W , Fang L , Zheng F , Zhan CG
Ref : Chemico-Biological Interactions , 203 :57 , 2013
Abstract :
PubMedSearch : Xue_2013_Chem.Biol.Interact_203_57
PubMedID: 22917637

Title : Cocaine metabolism accelerated by a re-engineered human butyrylcholinesterase - Sun_2002_J.Pharmacol.Exp.Ther_302_710
Author(s) : Sun H , Shen ML , Pang YP , Lockridge O , Brimijoin S
Ref : Journal of Pharmacology & Experimental Therapeutics , 302 :710 , 2002
Abstract :
PubMedSearch : Sun_2002_J.Pharmacol.Exp.Ther_302_710
PubMedID: 12130735
Gene_locus related to this paper: human-BCHE

Title : Re-engineering butyrylcholinesterase as a cocaine hydrolase - Sun_2002_Mol.Pharmacol_62_220
Author(s) : Sun H , Pang YP , Lockridge O , Brimijoin S
Ref : Molecular Pharmacology , 62 :220 , 2002
Abstract :
PubMedSearch : Sun_2002_Mol.Pharmacol_62_220
PubMedID: 12130672
Gene_locus related to this paper: human-BCHE

Title : Predicted Michaelis-Menten complexes of cocaine-butyrylcholinesterase. Engineering effective butyrylcholinesterase mutants for cocaine detoxication. - Sun_2001_J.Biol.Chem_276_9330
Author(s) : Sun H , El Yazal J , Lockridge O , Schopfer LM , Brimijoin S , Pang YP
Ref : Journal of Biological Chemistry , 276 :9330 , 2001
Abstract :
PubMedSearch : Sun_2001_J.Biol.Chem_276_9330
PubMedID: 11104759

Title : Stereoselective inhibition of human butyrylcholinesterase by phosphonothiolate analogs of (+)- and (-)-cocaine - Berkman_1997_Biochem.Pharmacol_54_1261
Author(s) : Berkman CE , Underiner GE , Cashman JR
Ref : Biochemical Pharmacology , 54 :1261 , 1997
Abstract :
PubMedSearch : Berkman_1997_Biochem.Pharmacol_54_1261
PubMedID: 9416977

Title : Overlapping drug interaction sites of human butyrylcholinesterase dissected by site-directed mutagenesis - Loewenstein-Lichtenstein_1996_Mol.Pharmacol_50_1423
Author(s) : Loewenstein-Lichtenstein Y , Glick D , Gluzman N , Sternfeld M , Zakut H , Soreq H
Ref : Molecular Pharmacology , 50 :1423 , 1996
Abstract :
PubMedSearch : Loewenstein-Lichtenstein_1996_Mol.Pharmacol_50_1423
PubMedID: 8967962
Gene_locus related to this paper: human-BCHE

Title : Hydrolysis of cocaine in human plasma by cholinesterase -
Author(s) : Stewart DJ , Inaba T , Tang BK , Kalow W
Ref : Life Sciences , 20 :1557 , 1977
PubMedID: 17804