Mitragynine

Mitragynine
Names
IUPAC name
Methyl (2E)-2-[(2S,4S,5S)-5-ethyl-12-methoxy-7,17-diazatetracyclo[8.7.0.0²,⁷.0¹¹,¹⁶]heptadeca-1(10),11(16),12,14-tetraen-4-yl]-3-methoxyprop-2-enoate
Identifiers
4098-40-2 N
3D model (Jmol) Interactive image
ChEMBL ChEMBL299031 YesY
ChemSpider 2298865 YesY
KEGG C09226 N
PubChem 3034396
UNII EP479K822J N
Properties
C23H30N2O4
Molar mass 398.4953 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Mitragynine is an indole-based opioid and the most abundant active alkaloid in the plant Mitragyna speciosa, commonly known as kratom[1] and biak-biak.[2] Dry kratom leaf contains roughly 1-6% mitragynine.[3]

Subjective perceptions

In spite of the fact that mitragynine has sometimes been touted and used as a “legal opioid,” few scientific studies have addressed the psychoactive properties of mitragynine.[4][5][6][7] Most of the available information is based on anecdotal reports and patient experiences. The general subjective effects of mitragynine have been summarized in various reviews and include improved mood and analgesia, with some subjects experiencing relaxation and others stimulation (paradoxical effects).[8]

Pharmacology

Mitragynine itself acts primarily via μ-opioid receptors, though its oxidation product mitragynine pseudoindoxyl, acts as an even more potent and selective μ-opioid agonist but with less affinity for δ or κ receptors.[9][10] Another alkaloid with a major contribution to the μ-opioid activity of the kratom plant is the related compound 7-hydroxymitragynine, which, while present in the plant in much smaller quantities than mitragynine, is a much more potent μ-opioid agonist. The extent to which this minor but more potent mu agonist constituent of the plant contributes to the subjective effects of Kratom consumption is still unclear.[11][12]

Pharmacokinetics

Mitragynine has been studied in chronic users. It undergoes extensive hepatic metabolism with linear kinetics and long half life.[13]

Detection in body fluids

Blood mitragynine concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally. Detection in body fluids is typically by liquid chromatography-mass spectrometry.[14][15]

Structure

It is structurally related to both the yohimbe alkaloids and, more distantly, voacangine. Chemically, mitragynine is 9-methoxy-corynantheidine.

Synthesis

The first total synthesis of mitragynine was reported by Takayama et al. in 1995.[16]

See also

References

  1. ↑ Jansen KL, Prast CJ (1988). "Ethnopharmacology of kratom and the Mitragyna alkaloids". J Ethnopharmacol. 23 (1): 115–9. doi:10.1016/0378-8741(88)90121-3. PMID 3419199.
  2. ↑ Raffa, RB; Beckett, JR; Brahmbhatt, VN; et al. (2013). "Orally active opioid compounds from a non-poppy source". J Med Chem. 56 (12): 4840–8. doi:10.1021/jm400143z.
  3. ↑ Kikura-Hanajiri, Ruri; Kawamura, Maiko; Maruyama, Takuro; Kitajima, Mariko; Takayama, Hiromitsu; Goda, Yukihiro (July 2009). "Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant "kratom" (Mitragyna speciosa) by LC-ESI-MS". Forensic Toxicology. 27 (2): 67–74. doi:10.1007/s11419-009-0070-5. ISSN 1860-8973.
  4. ↑ Jansen, KL; Prast, CJ (1988). "Ethnopharmacology of kratom and the Mitragyna alkaloids". J Ethnopharmacol. 23 (1): 115–119. doi:10.1016/0378-8741(88)90121-3. PMID 3419199.
  5. ↑ Suwanlert, S (1975). "A study of kratom eaters in Thailand". Bull Narc. 27 (3): 21–27.
  6. ↑ Jansen, KL; Prast, CJ (1988). "Psychoactive properties of mitragynine (kratom)". J Psychoactive Drugs. 20 (4): 455–457. doi:10.1080/02791072.1988.10472519.
  7. ↑ Shellard, EJ (1989). "Ethnopharmacology of kratom and the Mitragyna alkaloids". J Ethnopharmacol. 25 (1): 123–124. doi:10.1016/0378-8741(89)90053-6.
  8. ↑ Adkins, JE; Boyer, EW; McCurdy, CR (2011). "Mitragyna speciosa, a psychoactive tree from Southeast Asia with opioid activity". Curr Top Med Chem. 11 (9): 1165–1175. doi:10.2174/156802611795371305. PMID 21050173.
  9. ↑ Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D, Koyama F, Matsumoto K, Moriyama T, Yamamoto LT, Watanabe K, Murayama T, Horie S (April 2002). "Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands". J. Med. Chem. 45 (9): 1949–56. doi:10.1021/jm010576e. PMID 11960505.
  10. ↑ Yamamoto, Leonardo T.; Horie, Syunji; Takayama, Hiromitsu; Aimi, Norio; Sakai, Shin-ichiro; Yano, Shingo; Shan, Jie; Pang, Peter K. T.; Ponglux, Dhavadee; Watanabe, Kazuo (July 1999). "Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa". General Pharmacology: The Vascular System. 33 (1): 73–81. doi:10.1016/S0306-3623(98)00265-1. PMID 10428019.
  11. ↑ Vuppala PK, Jamalapuram S, Furr EB, McCurdy CR, Avery BA (Dec 2013). "Development and validation of a UPLC-MS/MS method for the determination of 7-hydroxymitragynine, a μ-opioid agonist, in rat plasma and its application to a pharmacokinetic study". Biomedical Chromatography. 27 (12): 1726–1732. doi:10.1002/bmc.2986. PMID 23893615.
  12. ↑ Takayama, Hiromitsu (August 2004). "Chemistry and Pharmacology of Analgesic Indole Alkaloids from the Rubiaceous Plant, Mitragyna speciosa". Chemical and Pharmaceutical Bulletin. 52 (8): 916–928. doi:10.1248/cpb.52.916. PMID 15304982.
  13. ↑ Trakulsrichai, Satariya; Sathirakul, Korbtham; Auparakkitanon, Saranya; Krongvorakul, Jatupon; Sueajai, Jetjamnong; Noumjad, Nantida; Sukasem, Chonlaphat; Wananukul, Winai (2015-04-29). "Pharmacokinetics of mitragynine in man". Drug Design, Development and Therapy. 9: 2421–2429. doi:10.2147/DDDT.S79658. ISSN 1177-8881. PMC 4425236Freely accessible. PMID 25995615.
  14. ↑ Le, David; Goggin, Melissa M.; Janis, Gregory C. (November–December 2012). "Analysis of Mitragynine and Metabolites in Human Urine for Detecting the Use of the Psychoactive Plant Kratom". Journal of Analytical Toxicology. 36 (9): 616–625. doi:10.1093/jat/bks073. ISSN 1945-2403. PMID 23024321.
  15. ↑ Baselt RC (2014). Disposition of toxic drugs and chemicals in man. Seal Beach, Calif.: Biomedical Publications. p. 1382. ISBN 978-0-9626523-9-4.
  16. ↑ Takayama H.; Maeda M.; Ohbayashi S.; Kitajima M.; Sakai S.-i.; Aimi N. (1995). "The First Total Synthesis of (−)-Mitragynine, An Analgesic Indole Alkaloid in Mitragyna speciosa". Tetrahedron Letters. 36 (51): 9337–9340. doi:10.1016/0040-4039(95)02022-H.

Further reading

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