Cocaine

Cocaine
Clinical data
Pronunciationkə(ʊ)ˈkeɪn
Trade namesNeurocaine,[1] Goprelto,[2] Numbrino,[3] others
Other namesCoke, blow, snow, crack (in free base form)
AHFS/Drugs.comMicromedex Detailed Consumer Information
License data
Dependence
liability
Physical: Low Psychological: High[4]
Addiction
liability
High[5]
Routes of
administration
Topical, by mouth, insufflation, intravenous, inhalation
Drug class
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability
MetabolismLiver, CYP3A4
MetabolitesNorcocaine, benzoylecgonine, cocaethylene
Onset of actionSeconds to minutes[12]
Duration of action20 to 90 minutes[12]
ExcretionKidney
Identifiers
  • Methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.000.030 Edit this at Wikidata
Chemical and physical data
FormulaC17H21NO4
Molar mass303.358 g·mol−1
3D model (JSmol)
Melting point98 °C (208 °F)
Boiling point187 °C (369 °F)
Solubility in water1.8g/L (22 °C)
  • CN1[C@H]2CC[C@@H]1[C@@H](C(OC)=O)[C@@H](OC(C3=CC=CC=C3)=O)C2
  • 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 checkY
  • Key:ZPUCINDJVBIVPJ-LJISPDSOSA-N checkY
Data page
Cocaine (data page)
 ☒NcheckY (what is this?)  (verify)

Cocaine (from French: cocaïne, from Spanish: coca, ultimately from Quechua: kúka)[13] is a tropane alkaloid that acts as a central nervous system (CNS) stimulant. As an extract, it is mainly used recreationally, and often illegally for its euphoric and rewarding effects. It is also used in medicine by Indigenous South Americans for various purposes and rarely, but more formally, as a local anaesthetic or diagnostic tool by medical practitioners in more developed countries. It is primarily obtained from the leaves of two Coca species native to South America: Erythroxylum coca and E. novogranatense.[14][15] After extraction from the plant, and further processing into cocaine hydrochloride (powdered cocaine), the drug is administered by being either snorted, applied topically to the mouth, or dissolved and injected into a vein. It can also then be turned into free base form (typically crack cocaine), in which it can be heated until sublimated and then the vapours can be inhaled.[12]

Cocaine stimulates the reward pathway in the brain.[15] Mental effects may include an intense feeling of happiness, sexual arousal, loss of contact with reality, or agitation.[12] Physical effects may include a fast heart rate, sweating, and dilated pupils.[12] High doses can result in high blood pressure or high body temperature.[16] Onset of effects can begin within seconds to minutes of use, depending on method of delivery, and can last between five and ninety minutes.[12] As cocaine also has numbing and blood vessel constriction properties, it is occasionally used during surgery on the throat or inside of the nose to control pain, bleeding, and vocal cord spasm.[17]

Cocaine crosses the blood–brain barrier via a proton-coupled organic cation antiporter[18][19] and (to a lesser extent) via passive diffusion across cell membranes.[20] Cocaine blocks the dopamine transporter,[21] inhibiting reuptake of dopamine from the synaptic cleft into the pre-synaptic axon terminal; the higher dopamine levels in the synaptic cleft increase dopamine receptor activation in the post-synaptic neuron,[22][23] causing euphoria and arousal.[24] Cocaine also blocks the serotonin transporter and norepinephrine transporter, inhibiting reuptake of serotonin and norepinephrine from the synaptic cleft into the pre-synaptic axon terminal and increasing activation of serotonin receptors and norepinephrine receptors in the post-synaptic neuron, contributing to the mental and physical effects of cocaine exposure.[6]

A single dose of cocaine induces tolerance to the drug's effects.[25] Repeated use is likely to result in addiction. Addicts who abstain from cocaine may experience craving and drug withdrawal symptoms, with depression, decreased libido, decreased ability to feel pleasure, and fatigue being most common.[15] Use of cocaine increases the overall risk of death, and intravenous use potentially increases the risk of trauma and infectious diseases such as blood infections and HIV through the use of shared paraphernalia. It also increases risk of stroke, heart attack, cardiac arrhythmia, lung injury (when smoked), and sudden cardiac death.[15][26] Illicitly sold cocaine can be adulterated with fentanyl, local anesthetics, levamisole, cornstarch, quinine, or sugar, which can result in additional toxicity.[27][28] In 2017, the Global Burden of Disease study found that cocaine use caused around 7,300 deaths annually.[29]

  1. ^ Nordegren T (2002). The A-Z Encyclopedia of Alcohol and Drug Abuse. Universal-Publishers. p. 461. ISBN 978-1-58112-404-0.
  2. ^ Cite error: The named reference Goprelto FDA label was invoked but never defined (see the help page).
  3. ^ Cite error: The named reference Numbrino FDA label was invoked but never defined (see the help page).
  4. ^ Ghodse H (2010). Ghodse's Drugs and Addictive Behaviour: A Guide to Treatment (4 ed.). Cambridge University Press. p. 91. ISBN 978-1-139-48567-8. Archived from the original on 10 September 2017.
  5. ^ Introduction to Pharmacology (3 ed.). Abingdon: CRC Press. 2007. pp. 222–223. ISBN 978-1-4200-4742-4. Archived from the original on 10 September 2017.
  6. ^ a b Azizi SA (December 2020). "Monoamines: Dopamine, Norepinephrine, and Serotonin, Beyond Modulation, "Switches" That Alter the State of Target Networks". The Neuroscientist. 28 (2): 121–143. doi:10.1177/1073858420974336. PMID 33292070. S2CID 228080727.
  7. ^ "DEA / Drug Scheduling". www.dea.gov. Archived from the original on 9 August 2017. Retrieved 7 August 2017.
  8. ^ a b Fattinger K, Benowitz NL, Jones RT, Verotta D (July 2000). "Nasal mucosal versus gastrointestinal absorption of nasally administered cocaine". European Journal of Clinical Pharmacology. 56 (4): 305–10. doi:10.1007/s002280000147. PMID 10954344. S2CID 20708443.
  9. ^ Barnett G, Hawks R, Resnick R (1981). "Cocaine pharmacokinetics in humans". Journal of Ethnopharmacology. 3 (2–3): 353–66. doi:10.1016/0378-8741(81)90063-5. PMID 7242115.
  10. ^ Jeffcoat AR, Perez-Reyes M, Hill JM, Sadler BM, Cook CE (1989). "Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking". Drug Metabolism and Disposition. 17 (2): 153–9. PMID 2565204.
  11. ^ Wilkinson P, Van Dyke C, Jatlow P, Barash P, Byck R (March 1980). "Intranasal and oral cocaine kinetics". Clinical Pharmacology and Therapeutics. 27 (3): 386–94. doi:10.1038/clpt.1980.52. PMID 7357795. S2CID 29851205.
  12. ^ a b c d e f Zimmerman JL (October 2012). "Cocaine intoxication". Critical Care Clinics. 28 (4): 517–26. doi:10.1016/j.ccc.2012.07.003. PMID 22998988.
  13. ^ "Cocaine". American Heritage Dictionary.
  14. ^ Plowman T (June 1982). "The identification of coca (Erythroxylum species): 1860–1910". Botanical Journal of the Linnean Society. 84 (4): 329–353. doi:10.1111/j.1095-8339.1982.tb00368.x.
  15. ^ a b c d Pomara C, Cassano T, D'Errico S, Bello S, Romano AD, Riezzo I, Serviddio G (2012). "Data available on the extent of cocaine use and dependence: biochemistry, pharmacologic effects and global burden of disease of cocaine abusers". Current Medicinal Chemistry. 19 (33): 5647–57. doi:10.2174/092986712803988811. PMID 22856655.
  16. ^ Connors NJ, Hoffman RS (November 2013). "Experimental treatments for cocaine toxicity: a difficult transition to the bedside". The Journal of Pharmacology and Experimental Therapeutics. 347 (2): 251–7. doi:10.1124/jpet.113.206383. PMID 23978563. S2CID 6767268.
  17. ^ Hamdan AL, Sataloff RT, Hawkshaw MJ (2022). "Topical Anesthesia in Office-Based Laryngeal Surgery". Office-Based Laryngeal Surgery. USA: Springer. pp. 123–137. doi:10.1007/978-3-030-91936-8_6. ISBN 978-3-030-91935-1.
  18. ^ Sachkova A, Doetsch DA, Jensen O, Brockmöller J, Ansari S (October 2021). "How do psychostimulants enter the human brain? Analysis of the role of the proton-organic cation antiporter". Biochemical Pharmacology. 192: 114751. doi:10.1016/j.bcp.2021.114751. PMID 34464621.
  19. ^ Tega Y, Tabata H, Kurosawa T, Kitamura A, Itagaki F, Oshitari T, Deguchi Y (January 2021). "Structural Requirements for Uptake of Diphenhydramine Analogs into hCMEC/D3 Cells Via the Proton-Coupled Organic Cation Antiporter". Journal of Pharmaceutical Sciences. 110 (1): 397–403. doi:10.1016/j.xphs.2020.09.001. PMID 32898521.
  20. ^ Chapy H, Smirnova M, André P, Schlatter J, Chiadmi F, Couraud PO, et al. (October 2014). "Carrier-mediated cocaine transport at the blood–brain barrier as a putative mechanism in addiction liability". The International Journal of Neuropsychopharmacology. 18 (1): pyu001. doi:10.1093/ijnp/pyu001. PMC 4368859. PMID 25539501.
  21. ^ Cheng MH, Block E, Hu F, Cobanoglu MC, Sorkin A, Bahar I (2015). "Insights into the Modulation of Dopamine Transporter Function by Amphetamine, Orphenadrine, and Cocaine Binding". Frontiers in Neurology. 6: 134. doi:10.3389/fneur.2015.00134. PMC 4460958. PMID 26106364.
  22. ^ Proebstl L, Kamp F, Manz K, Krause D, Adorjan K, Pogarell O, et al. (June 2019). "Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies". European Psychiatry. 59: 15–24. doi:10.1016/j.eurpsy.2019.03.003. PMID 30981746.
  23. ^ "How does cocaine produce its effects?".
  24. ^ Wise RA, Robble MA (January 2020). "Dopamine and Addiction". Annual Review of Psychology. 71 (1): 79–106. doi:10.1146/annurev-psych-010418-103337. PMID 31905114.
  25. ^ Ambre JJ, Belknap SM, Nelson J, Ruo TI, Shin SG, Atkinson AJ (July 1988). "Acute tolerance to cocaine in humans". Clinical Pharmacology and Therapeutics. 44 (1): 1–8. doi:10.1038/clpt.1988.104. PMID 3390996. S2CID 44253676.
  26. ^ Sordo L, Indave BI, Barrio G, Degenhardt L, de la Fuente L, Bravo MJ (September 2014). "Cocaine use and risk of stroke: a systematic review". Drug and Alcohol Dependence. 142: 1–13. doi:10.1016/j.drugalcdep.2014.06.041. PMID 25066468.
  27. ^ Goldstein RA, DesLauriers C, Burda AM (January 2009). "Cocaine: history, social implications, and toxicity--a review". Disease-a-Month. 55 (1): 6–38. doi:10.1016/j.disamonth.2008.10.002. PMID 19081448.
  28. ^ "Fentanyl-Adulterated Cocaine: Strategies To Address The New Normal". 25 April 2019.
  29. ^ Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, Abbastabar H, Abd-Allah F, Abdela J, Abdelalim A, Abdollahpour I, et al. (GBD 2017 Causes of Death Collaborators) (November 2018). "Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017". Lancet. 392 (10159): 1736–1788. doi:10.1016/S0140-6736(18)32203-7. PMC 6227606. PMID 30496103.