7-Hydroxymitragynine
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| Other names | 7α-Hydroxy-7H-mitragynine;[1] 9-Methoxycorynantheidine hydroxyindolenine[1] |
| Routes of administration | By mouth |
| Drug class | Opioid |
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| Metabolites | Mitragynine pseudoindoxyl |
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| Formula | C23H30N2O5 |
| Molar mass | 414.502 g·mol−1 |
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7-Hydroxymitragynine (7-OH) is a terpenoid indole alkaloid from the plant Mitragyna speciosa, commonly known as kratom.[2] It was first described in 1994[3] and is a natural product derived from mitragynine present in the kratom leaf. 7-OH binds to opioid receptors like mitragynine, but research suggests that 7-OH binds with greater efficacy.[4]
Dependence and withdrawal
[edit]Pharmacology
[edit]7-Hydroxymitragynine, like mitragynine, appears to be a mixed opioid receptor agonist/antagonist, acting as a partial agonist at μ-opioid receptors and as a competitive antagonist at δ- and κ-opioid receptors.[5][6] Evidence suggests that 7-OH is more potent than both mitragynine and morphine. 7-OH does not activate the β-arrestin pathway like traditional opioids, meaning symptoms such as respiratory depression, constipation and sedation are much less pronounced.[5]
7-OH is generated from mitragynine in vivo by hepatic metabolism and may account for a significant portion of the effects traditionally associated with mitragynine. Although 7-OH occurs naturally in kratom leaves, it does so in such low amounts that any ingested 7-OH is inconsequential compared to the 7-OH generated in the body.[5]
Metabolism
[edit]7-Hydroxymitragynine can convert into mitragynine up to 45% in human liver microsomes over a two-hour incubation and was degraded up to 27% in simulated gastric fluid and degraded up to 6% in simulated intestinal fluid.[7] 7-Hydroxymitragynine can metabolize to mitragynine pseudoindoxyl in the blood but not in the liver.[8][9] Interestingly, this even more potent opioid was revealed to exist in a mixture of stereoisomers in biological systems.[9]
| Compound | Affinities (Ki) | Ratio | Ref | ||
|---|---|---|---|---|---|
| MOR | DOR | KOR | MOR:DOR:KOR | ||
| 7-Hydroxymitragynine | 13.5 | 155 | 123 | 1:11:9 | [10] |
| Mitragynine | 7.24 | 60.3 | 1,100 | 1:8:152 | [10] |
| Mitragynine pseudoindoxyl | 0.087 | 3.02 | 79.4 | 1:35:913 | [10] |
See also
[edit]- Ajmalicine
- Mitragynine
- Mitragynine pseudoindoxyl
- Mitraphylline
- β-Prodine - molecule overlaying 7-hydroxymitragynine's opioid QSAR (Quantitative structure-activity relationship)
References
[edit]- ^ a b Chemical Abstracts Service: Columbus, OH, 2004; RN 174418-82-7 (accessed via SciFinder Scholar, version 2007.3; November 30, 2011)
- ^ Matsumoto K, Horie S, Ishikawa H, Takayama H, Aimi N, Ponglux D, Watanabe K (March 2004). "Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa". Life Sciences. 74 (17): 2143–2155. doi:10.1016/j.lfs.2003.09.054. PMID 14969718.
- ^ Ponglux D, Wongseripipatana S, Takayama H, Kikuchi M, Kurihara M, Kitajima M, et al. (December 1994). "A New Indole Alkaloid, 7 alpha-Hydroxy-7H-mitragynine, from Mitragyna speciosa in Thailand". Planta Medica. 60 (6): 580–581. doi:10.1055/s-2006-959578. PMID 17236085. S2CID 260252538.
- ^ Kruegel AC, Grundmann O (May 2018). "The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse". Neuropharmacology. 134 (Pt A): 108–120. doi:10.1016/j.neuropharm.2017.08.026. PMID 28830758. S2CID 24009429.
- ^ a b c Eastlack SC, Cornett EM, Kaye AD (June 2020). "Kratom-Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review". Pain and Therapy. 9 (1): 55–69. doi:10.1007/s40122-020-00151-x. PMC 7203303. PMID 31994019.
- ^ Chang-Chien GC, Odonkor CA, Amorapanth P (2017). "Is Kratom the New 'Legal High' on the Block?: The Case of an Emerging Opioid Receptor Agonist with Substance Abuse Potential". Pain Physician. 20 (1): E195–E198. doi:10.36076/ppj.2017.1.E195. PMID 28072812.
- ^ Manda V, Avula B, Ali Z, Khan I, Walker L, Khan S (2014). "Evaluation of in Vitro Absorption, Distribution, Metabolism, and Excretion (ADME) Properties of Mitragynine, 7-Hydroxymitragynine, and Mitraphylline". Planta Medica. 80 (7): 568–576. doi:10.1055/s-0034-1368444. PMID 24841968.
- ^ Váradi A, Marrone GF, Palmer TC, Narayan A, Szabó MR, Le Rouzic V, et al. (September 2016). "Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2". Journal of Medicinal Chemistry. 59 (18): 8381–8397. doi:10.1021/acs.jmedchem.6b00748. PMC 5344672. PMID 27556704.
- ^ a b Kamble SH, León F, King TI, Berthold EC, Lopera-Londoño C, Siva Rama Raju K, et al. (December 2020). "Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy". ACS Pharmacology & Translational Science. 3 (6): 1063–1068. doi:10.1021/acsptsci.0c00075. PMC 7737207. PMID 33344889.
- ^ a b c Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D, et al. (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". Journal of Medicinal Chemistry. 45 (9): 1949–1956. doi:10.1021/jm010576e. PMID 11960505.
Further reading
[edit]- Takayama H (August 2004). "Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa". Chemical & Pharmaceutical Bulletin. 52 (8): 916–928. doi:10.1248/cpb.52.916. PMID 15304982.