Thebaine

Thebaine (paramorphine), also known as codeine methyl enol ether, is an opiate alkaloid, its name coming from the Greek Θῆβαι, Thēbai (Thebes), an ancient city in Upper Egypt. A minor constituent of opium, thebaine is chemically similar to both morphine and codeine, but has stimulatory rather than depressant effects. At high doses, it causes convulsions similar to strychnine poisoning. The synthetic enantiomer (+)-thebaine does show analgesic effects apparently mediated through opioid receptors, unlike the inactive natural enantiomer (−)-thebaine.[3] While thebaine is not used therapeutically, it is the main alkaloid extracted from Papaver bracteatum (Iranian opium / Persian poppy) and can be converted industrially into a variety of compounds, including hydrocodone, hydromorphone, oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, buprenorphine, butorphanol and etorphine.[4]

Thebaine
Skeletal formula
Ball-and-stick model
Names
IUPAC name
3,6-Dimethoxy-17-methyl-6,7,8,14-tetradehydro-4,5α-epoxymorphinan
Systematic IUPAC name
(4R,7aR,12bS)-7,9-Dimethoxy-3-methyl-2,3,4,7a-tetrahydro-1H-4,12-methano[1]benzofuro[3,2-e]isoquinoline
Other names
Paramorphine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.003.713
KEGG
MeSH Thebaine
UNII
  • InChI=1S/C19H21NO3/c1-20-9-8-19-12-5-7-15(22-3)18(19)23-17-14(21-2)6-4-11(16(17)19)10-13(12)20/h4-7,13,18H,8-10H2,1-3H3/t13-,18+,19+/m1/s1 checkY
    Key: FQXXSQDCDRQNQE-VMDGZTHMSA-N checkY
  • InChI=1S/C19H21NO3/c1-20-9-8-19-12-5-7-15(22-3)18(19)23-17-14(21-2)6-4-11(16(17)19)10-13(12)20/h4-7,13,18H,8-10H2,1-3H3/t13-,18+,19+/m1/s1
    Key: FQXXSQDCDRQNQE-VMDGZTHMBG
  • Key: FQXXSQDCDRQNQE-VMDGZTHMSA-N
  • COC1=CC=C2[C@@H](C3)N(C)CC[C@@]24C5=C3C=CC(OC)=C5O[C@@H]14
Properties
C19H21NO3
Molar mass 311.37 g/mol
Pharmacology
Low[1]
Pharmacokinetics:
O-demethylation[2]
Legal status
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)
Infobox references

Thebaine is controlled under international law, is listed as a Class A drug under the Misuse of Drugs Act 1971 in the United Kingdom, is controlled as an analog of a Schedule II drug per the Analog Act in the United States, and is controlled with its derivatives and salts, as a Schedule I substance of the Controlled Drugs and Substances Act in Canada.[5] The 2013 US Drug Enforcement Administration (DEA) aggregate manufacturing quota for thebaine (ACSCN 9333) was unchanged from the previous year at 145 metric tons.

This alkaloid is biosynthetically related to salutaridine, oripavine, morphine and reticuline.[6]

In 2012 there was an amounted 146,000 kilograms of thebaine produced.[7] In 2013, Australia was the main producer of poppy straw rich in thebaine, followed by Spain and then France. By 2017, worldwide thebaine production dropped to 2,008 kg.[8] Together, those three countries accounted for about 99 per cent of global production of such poppy straw. The Papaver bracteatum seed capsules are the primary source of thebaine, with the stem additionally yielding a significant amount.[9][10]

The Canberra Times of 16 November 2022[11] reported that four batches of Hoyts brand poppy seeds were being recalled due to unusually high levels of thebaine, and that at least twelve people in New South Wales had required medical attention after ingesting them. As of 15 November 2022, Food Standards Australia New Zealand (FSANZ) is coordinating a national recall of a number of poppy seed products due to the potential presence of thebaine.[12]

Synthesis

Research

Thebaine has been produced by GMO E. coli.[13]

See also

References
  1. WHO Advisory Group (1980). "The dependence potential of thebaine". Bulletin on Narcotics. 32 (1): 45–54. PMID 6778542. Archived from the original on 2014-05-12.
  2. Mikus, G.; Somogyi, A. A.; Bochner, F.; Eichelbaum, M. (1991). "Thebaine O-demethylation to oripavine: Genetic differences between two rat strains". Xenobiotica. 21 (11): 1501–9. doi:10.3109/00498259109044400. PMID 1763524.
  3. Aceto, M. D.; Harris, L. S.; Abood, M. E.; Rice, K. C. (1999). "Stereoselective μ- and δ-opioid receptor-related antinociception and binding with (+)-thebaine". European Journal of Pharmacology. 365 (2–3): 143–7. doi:10.1016/S0014-2999(98)00862-0. PMID 9988096.
  4. "DEA Diversion Control Division" (PDF). Archived (PDF) from the original on 2014-06-11. Retrieved 2014-07-12.
  5. "Controlled Drugs and Substances Act". Justice Laws Website. Government of Canada. 2012-11-06. Archived from the original on 2013-11-22. Retrieved 2014-01-12.
  6. Novak, B.; Hudlicky, T.; Reed, J.; Mulzer, J.; Trauner, D. (2000). "Morphine Synthesis and Biosynthesis-An Update" (PDF). Current Organic Chemistry. 4 (3): 343–62. CiteSeerX 10.1.1.515.9096. doi:10.2174/1385272003376292. Archived (PDF) from the original on 2012-06-19.
  7. Narcotic Drugs 2014 (PDF). INTERNATIONAL NARCOTICS CONTROL BOARD. 2015. p. 21. ISBN 9789210481571. Archived (PDF) from the original on 2015-06-02.
  8. "International Narcotics Control Board Narcotic Drugs 2018" (PDF). INCB.org.
  9. "Narcotic Drugs: Estimated World Requirements for 2015; Statistics for 2013" (PDF). International Narcotics Control Board. United Nations International Narcotics Control Board. 2015. p. 151 ff. Archived (PDF) from the original on June 2, 2015. Retrieved January 7, 2016.
  10. Whoriskey, Peter. "Johnson & Johnson companies used a super poppy to make narcotics for popular opioid pills - Washington Post". Washington Post. Retrieved 27 March 2020.
  11. "DEA Diversion Control Division". Archived (PDF) from the original on 2014-06-11. Retrieved 2014-07-12.
  12. "National Recall of Poppy Seeds". Food Standards Australia New Zealand. Food Standards Australia New Zealand (FSANZ). Retrieved 21 November 2022.
  13. "Genetically modified E. coli pump out morphine precursor: Bacteria yield 300 times more opiates than yeast". ScienceDaily.
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