Norcocaine

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Norcocaine
Norcocaine.png
Systematic (IUPAC) name
methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-azabicyclo[3.2.1]octane-2-carboxylate
Clinical data
Legal status
?
Identifiers
CAS number 18717-72-1 YesY
ATC code None
PubChem CID 644007
ChemSpider 559083 YesY
Chemical data
Formula C16H19NO4 
Mol. mass 289.326
 YesY (what is this?)  (verify)
Not to be confused with "Nocaine"

Norcocaine is a minor metabolite of cocaine. It is the only confirmed pharmacologically active metabolite of cocaine,[1] although salicylmethylecgonine is also speculated to be an active metabolite. The local anesthetic potential of norcocaine has been shown to be higher than that of cocaine,[2][3] however cocaine continues to be more widely used. Norcocaine used for research purposes is typically synthesized from cocaine. Several methods for the synthesis have been described.[4][5]

Legal status[edit]

The legal status of norcocaine is somewhat ambiguous. The US DEA does not list norcocaine as a controlled substance.[6] However, some suppliers of norcocaine, like Sigma-Aldrich, consider the drug to be a Schedule II drug (same as cocaine) for the purpose of their own sales.[7]

Regulatory status[edit]

Norcoaine has never been approved for use as a drug in the United States and is not listed on the FDA Orange Book of Approved Drug Products.[8]

Toxicity[edit]

The LD50 of norcocaine has been studied in mice. When administered by the intraperitoneal route the LD50 in mice was 40 mg/kg.[9]

Sales[edit]

Norcocaine is not marketed in the Unites States as a pharmaceutical. Lidocaine is a local anesthetic with similar effects to norcocaine.[10] For the third quarter of 2013, lidocaine sales were about $225 million. This placed lidocaine as the #71 drug for sales in the US for that quarter.[11] If norcocaine were successfully marketed, it would likely be a competitor in the same market. Since norcocaine was first discussed in literature as early as 1974,[12] patent protection of norcocaine as drug product would not currently be possible. This makes it unlikely that norcocaine will ever be taken to clinical trials. A search of all United States Patent and Trademark Office patents found five patents listing norcocaine in their claims.[13] None of these patents pertain to the use of norcocaine as an anesthetic drug.

Role in hair drug testing controversy[edit]

Some researchers have suggested that hair drug testing for cocaine use should include testing for metabolites like norcocaine.[14] The basis for this suggestion is the potential for external contamination of hair during testing. There is considerable debate about whether current means of washing hair samples are sufficient for removing external contamination. Some researchers state the methods are sufficient,[15][16] while others state the residual contamination may result in a false positive test.[14][17][18][19] Metabolites of cocaine, like norcocaine, in a addition to cocaine, should be present in samples from drug users. Authors have stated that the metabolites should be present in any samples declared positive.[14] Issues arise because the metabolites are present in only low concentrations. If the metabolites are present, it is possible for them to be from other contamination.[20]

References[edit]

  1. ^ Virtual Mass Spectrometry Laboratory: Cocaine in Hair
  2. ^ Wang, Q; et al (January 2001). "Contribution of the active metabolite, norcocaine, to cocaine's effects after intravenous and oral administration in rats: pharmacodynamics". Psychopharmacology 153 (3): 341–352. doi:10.1007/s002130000568. PMID 11271407. 
  3. ^ Just, WW; J Hoyer (January 1977). "The local anesthetic potency of norcocaine, a metabolite of cocaine". Cellular and Molecular Life Sciences (Basel: Birkhäuser) 33 (1): 70–71. doi:10.1007/BF01936761. PMID 836425. 
  4. ^ Stenberg, VI; et. al. (April 1976). "An improved synthesis of norcocaine". Journal of Heterocyclic Chemistry 13 (2): 363–364. doi:10.1002/jhet.5570130231. 
  5. ^ Lazer, ES; et. al. (December 1978). "Synthesis and biological activity of cocaine analogs I: N-alkylated norcocaine derivatives". Journal of Pharmaceutical Science 67 (12): 1656–1658. doi:10.1002/jps.2600671204. 
  6. ^ "Controlled Substances". dea.gov. United States Drug Enforcement Administration, United States Department of Justice. 9 September 2014. Retrieved 8 December 2014. 
  7. ^ "Norcocaine". sigmaaldrich.com. Sigma-Aldrich Co. LLC. Retrieved 8 December 2014. 
  8. ^ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". fda.gov. U.S. Food and Drug Administration. Retrieved 8 December 2014. 
  9. ^ Evans, MA; T Morarity (January 1980). "Analysis of cocaine and cocaine metabolites by high pressure liquid chromatography". Journal of Analytical Toxicology 4 (1): 19–22. doi:10.1093/jat/4.1.19. 
  10. ^ Fresenius Kabi USA, LLC (10 November 2014). "Xylocaine MPF". medlibrary.org. Mulhauser Consulting, Ltd. Retrieved 8 December 2014. 
  11. ^ "U.S. Pharmaceutical Sales - Q4 2013". drugs.com. Drugsite Trust. February 2014. Retrieved 8 December 2014. 
  12. ^ Mirsa, AL; et. al. (1974). "Identification of norcocaine as a metabolit of [H-3]-cocaine in rat-brain". Experientia 30 (11): 1312–1314. 
  13. ^ uspto.gov. United States Patent and Trademark Office http://patft.uspto.gov/netahtml/PTO/search-bool.html |url= missing title (help). Retrieved 8 December 2014. 
  14. ^ a b c Cone, EJ; et. al. (1991). "Testing human hair for drugs of abuse. II. Identification of unique cocaine metabolites in hair of drug abusers and evaluation of decontamination procedures". J Anal Toxicology 15 (5): 250–255. 
  15. ^ Koren, G; et. al. (1992). "Differentiation between systemic exposure and external contamination". J Clin Pharmacol 32 (7): 671–675. 
  16. ^ Baumgartner, WA; Hill, VA (1992). "Hair analysis for drugs of abuse: Decontamination issues.". Recent Developments in Therapeutic Drug Monitoring and Clinical Toxicology. 
  17. ^ Henderson, GL; et. al. (23 September 1991). "Effect of External Contamination on the Analysis of Hair for Cocaine". Paper presented at the Joint Meeting of Forensic Toxicologists and the Canadian Society of Forensic Scientists, Montreal, Quebec, Canada. 
  18. ^ Welch, MJ; et. al. (1993). "Hair analysis for drugs of abuse: Evaluation of analytical methods, environmental issues, and development of reference materials". J Anal Toxicol 17 (7): 309–398. 
  19. ^ Blank, DL; Kidwell, DA (1993). "External contamination of hair by cocaine: An issue in forensic interpretation". Forensic Sci Int 63 (1-3): 145–156. 
  20. ^ Janzen, K (1992). "Concerning norcocaine, ethylbenzoylecgonine, and the identification of cocaine use in human hair". J Anal Toxicol 16 (6): 402.