Cocaine: Uses, Interactions, Mechanism of Action | DrugBank Online

Step 1

Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT: Cocaine in herbal tea. JAMA. 1986 Jan 3;255(1):40. [Article] Volkow ND, Wang GJ, Fischman MW, Foltin R, Fowler JS, Franceschi D, Franceschi M, Logan J, Gatley SJ, Wong C, Ding YS, Hitzemann R, Pappas N: Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain. Life Sci. 2000 Aug 11;67(12):1507-15. [Article] Dimitrijevic N, Dzitoyeva S, Manev H: An automated assay of the behavioral effects of cocaine injections in adult Drosophila. J Neurosci Methods. 2004 Aug 30;137(2):181-4. [Article] Uz T, Akhisaroglu M, Ahmed R, Manev H: The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice. Neuropsychopharmacology. 2003 Dec;28(12):2117-23. [Article] McClung CA, Sidiropoulou K, Vitaterna M, Takahashi JS, White FJ, Cooper DC, Nestler EJ: Regulation of dopaminergic transmission and cocaine reward by the Clock gene. Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9377-81. Epub 2005 Jun 20. [Article] FDA Approved Products: Numbrino (cocaine hydrochloride) nasal solution [Link] FDA Approved Products: Goprelto (cocaine hydrochloride) nasal solution [Link] DailyMed: Cocaine hydrochloride solution [Link]

Step 2

Wilson JM, Levey AI, Bergeron C, Kalasinsky K, Ang L, Peretti F, Adams VI, Smialek J, Anderson WR, Shannak K, Deck J, Niznik HB, Kish SJ: Striatal dopamine, dopamine transporter, and vesicular monoamine transporter in chronic cocaine users. Ann Neurol. 1996 Sep;40(3):428-39. [Article] Kim DI, Schweri MM, Deutsch HM: Synthesis and pharmacology of site specific cocaine abuse treatment agents: 8-substituted isotropane (3-azabicyclo[3.2.1]octane) dopamine uptake inhibitors. J Med Chem. 2003 Apr 10;46(8):1456-64. [Article] Rothman RB, Baumann MH, Dersch CM, Appel J, Houghten RA: Discovery of novel peptidic dopamine transporter ligands by screening a positional scanning combinatorial hexapeptide library. Synapse. 1999 Sep 1;33(3):239-46. [Article] Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article] Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [Article] Verma V: Classic Studies on the Interaction of Cocaine and the Dopamine Transporter. Clin Psychopharmacol Neurosci. 2015 Dec 31;13(3):227-38. doi: 10.9758/cpn.2015.13.3.227. [Article]

Step 3

Galli A, DeFelice LJ, Duke BJ, Moore KR, Blakely RD: Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants. J Exp Biol. 1995 Oct;198(Pt 10):2197-212. [Article] Burchett SA, Bannon MJ: Serotonin, dopamine and norepinephrine transporter mRNAs: heterogeneity of distribution and response to 'binge' cocaine administration. Brain Res Mol Brain Res. 1997 Oct 3;49(1-2):95-102. [Article] Zhao Y, Sun L: Perinatal cocaine exposure reduces myocardial norepinephrine transporter function in the neonatal rat. Neurotoxicol Teratol. 2004 May-Jun;26(3):443-50. [Article] Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article] Siegel GJ, Agranoff BW, Albers RW et al. (1999). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott Williams.

Step 4

Wright SN, Wang SY, Xiao YF, Wang GK: State-dependent cocaine block of sodium channel isoforms, chimeras, and channels coexpressed with the beta1 subunit. Biophys J. 1999 Jan;76(1 Pt 1):233-45. [Article] Crumb WJ Jr, Clarkson CW: Characterization of cocaine-induced block of cardiac sodium channels. Biophys J. 1990 Mar;57(3):589-99. doi: 10.1016/S0006-3495(90)82574-1. [Article] Siegel GJ, Agranoff BW, Albers RW et al. (1999). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott Williams.

Step 5

Patkar AA, Berrettini WH, Hoehe M, Thornton CC, Gottheil E, Hill K, Weinstein SP: Serotonin transporter polymorphisms and measures of impulsivity, aggression, and sensation seeking among African-American cocaine-dependent individuals. Psychiatry Res. 2002 Jun 1;110(2):103-15. [Article] Barker EL, Moore KR, Rakhshan F, Blakely RD: Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter. J Neurosci. 1999 Jun 15;19(12):4705-17. [Article] Corey JL, Quick MW, Davidson N, Lester HA, Guastella J: A cocaine-sensitive Drosophila serotonin transporter: cloning, expression, and electrophysiological characterization. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1188-92. [Article] Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article] Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [Article] Siegel GJ, Agranoff BW, Albers RW et al. (1999). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott Williams.

Step 6

Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article] Sharkey J, Ritz MC, Schenden JA, Hanson RC, Kuhar MJ: Cocaine inhibits muscarinic cholinergic receptors in heart and brain. J Pharmacol Exp Ther. 1988 Sep;246(3):1048-52. [Article]

Step 7

Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [Article] Sharkey J, Ritz MC, Schenden JA, Hanson RC, Kuhar MJ: Cocaine inhibits muscarinic cholinergic receptors in heart and brain. J Pharmacol Exp Ther. 1988 Sep;246(3):1048-52. [Article]

Step 8

Navarro G, Moreno E, Aymerich M, Marcellino D, McCormick PJ, Mallol J, Cortes A, Casado V, Canela EI, Ortiz J, Fuxe K, Lluis C, Ferre S, Franco R: Direct involvement of sigma-1 receptors in the dopamine D1 receptor-mediated effects of cocaine. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18676-81. doi: 10.1073/pnas.1008911107. Epub 2010 Oct 18. [Article] Sharkey J, Ritz MC, Schenden JA, Hanson RC, Kuhar MJ: Cocaine inhibits muscarinic cholinergic receptors in heart and brain. J Pharmacol Exp Ther. 1988 Sep;246(3):1048-52. [Article] Narayanan S, Mesangeau C, Poupaert JH, McCurdy CR: Sigma receptors and cocaine abuse. Curr Top Med Chem. 2011;11(9):1128-50. doi: 10.2174/156802611795371323. [Article] Yasui Y, Su TP: Potential Molecular Mechanisms on the Role of the Sigma-1 Receptor in the Action of Cocaine and Methamphetamine. J Drug Alcohol Res. 2016 Feb 20;5. doi: 10.4303/jdar/235970. [Article]

Step 9

Brzezinski MR, Spink BJ, Dean RA, Berkman CE, Cashman JR, Bosron WF: Human liver carboxylesterase hCE-1: binding specificity for cocaine, heroin, and their metabolites and analogs. Drug Metab Dispos. 1997 Sep;25(9):1089-96. [Article]

Step 10

Ladona MG, Gonzalez ML, Rane A, Peter RM, de la Torre R: Cocaine metabolism in human fetal and adult liver microsomes is related to cytochrome P450 3A expression. Life Sci. 2000 Dec 15;68(4):431-43. [Article] Chen X, Zheng X, Zhan M, Zhou Z, Zhan CG, Zheng F: Metabolic Enzymes of Cocaine Metabolite Benzoylecgonine. ACS Chem Biol. 2016 Aug 19;11(8):2186-94. doi: 10.1021/acschembio.6b00277. Epub 2016 Jun 9. [Article] Flockhart Table of Drug Interactions [Link] FDA Approved Products: Numbrino (cocaine hydrochloride) nasal solution [Link]

Step 11

Shen H, He MM, Liu H, Wrighton SA, Wang L, Guo B, Li C: Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. Drug Metab Dispos. 2007 Aug;35(8):1292-300. doi: 10.1124/dmd.107.015354. Epub 2007 Apr 30. [Article]

Step 12

Chen Y, Goldstein JA: The transcriptional regulation of the human CYP2C genes. Curr Drug Metab. 2009 Jul;10(6):567-78. Epub 2009 Jul 15. [Article] Malaplate-Armand C, Ferrari L, Masson C, Visvikis-Siest S, Lambert H, Batt AM: Down-regulation of astroglial CYP2C, glucocorticoid receptor and constitutive androstane receptor genes in response to cocaine in human U373 MG astrocytoma cells. Toxicol Lett. 2005 Dec 15;159(3):203-11. doi: 10.1016/j.toxlet.2005.04.005. Epub 2005 Sep 26. [Article]

Step 13

Grasing K, Mathur D, DeSouza C, Newton TF, Moody DE, Sturgill M: Cocaine cardiovascular effects and pharmacokinetics after treatment with the acetylcholinesterase inhibitor donepezil. Am J Addict. 2016 Aug;25(5):392-9. doi: 10.1111/ajad.12402. Epub 2016 Jul 8. [Article] Schwartz HJ, Johnson D: In vitro competitive inhibition of plasma cholinesterase by cocaine: normal and variant genotypes. J Toxicol Clin Toxicol. 1996;34(1):77-81. doi: 10.3109/15563659609020237. [Article] FDA Approved Products: Numbrino (cocaine hydrochloride) nasal solution [Link]

Step 14

Brzezinski MR, Spink BJ, Dean RA, Berkman CE, Cashman JR, Bosron WF: Human liver carboxylesterase hCE-1: binding specificity for cocaine, heroin, and their metabolites and analogs. Drug Metab Dispos. 1997 Sep;25(9):1089-96. [Article] FDA Approved Products: Numbrino (cocaine hydrochloride) nasal solution [Link]

Step 15

Edwards DJ, Bowles SK: Protein binding of cocaine in human serum. Pharm Res. 1988 Jul;5(7):440-2. doi: 10.1023/a:1015992502509. [Article] Parker RB, Williams CL, Laizure SC, Lima JJ: Factors affecting serum protein binding of cocaine in humans. J Pharmacol Exp Ther. 1995 Nov;275(2):605-10. [Article]

Step 16

Grundemann D, Koster S, Kiefer N, Breidert T, Engelhardt M, Spitzenberger F, Obermuller N, Schomig E: Transport of monoamine transmitters by the organic cation transporter type 2, OCT2. J Biol Chem. 1998 Nov 20;273(47):30915-20. [Article]

Step 17

Grundemann D, Koster S, Kiefer N, Breidert T, Engelhardt M, Spitzenberger F, Obermuller N, Schomig E: Transport of monoamine transmitters by the organic cation transporter type 2, OCT2. J Biol Chem. 1998 Nov 20;273(47):30915-20. [Article] Crits-Christoph P, Newberg A, Wintering N, Ploessl K, Gibbons MB, Ring-Kurtz S, Gallop R, Present J: Dopamine transporter levels in cocaine dependent subjects. Drug Alcohol Depend. 2008 Nov 1;98(1-2):70-6. doi: 10.1016/j.drugalcdep.2008.04.014. Epub 2008 Jun 20. [Article] Mash DC, Pablo J, Ouyang Q, Hearn WL, Izenwasser S: Dopamine transport function is elevated in cocaine users. J Neurochem. 2002 Apr;81(2):292-300. doi: 10.1046/j.1471-4159.2002.00820.x. [Article]