Mitragynine

Mitragynine
Names
IUPAC name
(E)-2-[(2S,3S)-3-ethyl-8-methoxy-1,2,3,4,6,7,12,12b- octahydroindolo[3,2-h]quinolizin-2-yl]-3- methoxyprop-2-enoic acid methyl ester
Identifiers
6202-22-8 N
ChEMBL ChEMBL299031 YesY
ChemSpider 2298865 YesY
Jmol interactive 3D Image
PubChem 3034396
Properties
C23H30N2O4
Molar mass 398.495
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, an indole alkaloid, is the most abundant active alkaloid in the plant Mitragyna speciosa, commonly known as Kratom[1] and "Biak-Biak".[2]

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.[3][4][5][6] 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).[7]

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.[8][9] 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.[10][11]

Pharmacokinetics

Mitragynine has been studied in chronic users. It undergoes extensive hepatic metabolism with linear kinetics and long half life.[12] A large volume of distribution with two compartments is seen.

Discovery

Mitragynine was isolated in 1907 by D. Hooper, a process repeated in 1921 by E. Field who gave the alkaloid its name. Its structure was first fully determined in 1964 by D. Zacharias, R. Rosenstein and E. Jeffrey.[13]

Structure

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

Dose

Dry kratom leaf contains roughly 1-6% mitragynine.[14] A typical dose ranges from 15 mg to 65 mg. A notable distinction between mitragynine and traditional opioids is that mitragynine does not cause hypoventilation (respiratory depression) and therefore does not carry the primary safety risk associated with traditional opioids, most likely due to its agonism of the δ-opioid receptor.

Synthesis

The first total synthesis of mitragynine was reported by Takayama et al. in 1995.[15]

Chemical properties

Physically the freebase is a white, amorphous powder. It is soluble in alcohol, chloroform and acetic acid.

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. ↑ 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.
  4. ↑ Suwanlert, S (1975). "A study of kratom eaters in Thailand". Bull Narc. 27 (3): 21–27.
  5. ↑ Jansen, KL; Prast, CJ (1988). "Psychoactive properties of mitragynine (kratom)". J Psychoactive Drugs 20 (4): 455–457. doi:10.1080/02791072.1988.10472519.
  6. ↑ Shellard, EJ (1989). "Ethnopharmacology of kratom and the Mitragyna alkaloids". J Ethnopharmacol 25 (1): 123–124. doi:10.1016/0378-8741(89)90053-6.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Yamamoto, L. T.; Horie, S.; Takayama, H.; Aimi, N.; Sakai, S.; Yano, S.; Shan, J.; Pang, P. K.; Ponglux, D.; Watanabe, K. (1999). "Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa". General pharmacology 33 (1): 73–81. doi:10.1016/S0306-3623(98)00265-1. PMID 10428019.
  10. ↑ 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.
  11. ↑ Takayama H (August 2004). "Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa". Chem. Pharm. Bull. 52 (8): 916–28. doi:10.1248/cpb.52.916. PMID 15304982.
  12. ↑ 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 4425236. PMID 25995615.
  13. ↑ Kratom, 2014, retrieved 21 April 2014
  14. ↑ Kikura-Hanaji, Ruri; Kawamura, Maiko; Maruyama,Takuro; Kitajima, Mariko; Takayama, Hiromitsu; Goda,Yukihiro (1 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. Retrieved 23 June 2013.
  15. ↑ 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.

External links

Further reading

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