7-Hydroxymitragynine

7-Hydroxymitragynine is a terpenoid indole alkaloid from the plant Mitragyna speciosa, commonly known as kratom.[3] It is often referred to as ‘7-OH’. It was first described in 1994[4] and is a natural product derived from the mitragynine present in the kratom leaf. It is considered an oxidized derivative and active metabolite of mitragynine.[5] 7-OH binds to opioid receptors like mitragynine, but research suggests that 7-OH binds with greater potency[6] and contributes heavily to the analgesic activity of mitragynine as a metabolite.[7]

7-Acetoxymitragynine
7-Hydroxymitragynine
Stereo, Kekulé, skeletal formula of 7-hydroxymitragynine with an explicit hydrogen added
7-Hydroxymitragynine is a terpenoid indole alkaloid from the plant Mitragyna speciosa, commonly known as Kratom.
Names
Systematic IUPAC name
Methyl (2E)-2-[(2S,3S,7aS,12bS)-3-ethyl-7a-hydroxy-8-methoxy-1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl]-3-methoxyprop-2-enoate
Other names
7α-Hydroxy-7H-mitragynine;[1] 9-Methoxycorynantheidine hydroxyindolenine[1]
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
UNII
  • InChI=1S/C23H30N2O5/c1-5-14-12-25-10-9-23(27)20-17(7-6-8-19(20)29-3)24-21(23)18(25)11-15(14)16(13-28-2)22(26)30-4/h6-8,13-15,18,27H,5,9-12H2,1-4H3/b16-13+/t14-,15+,18+,23+/m1/s1 checkY
    Key: RYENLSMHLCNXJT-CYXFISRXSA-N checkY
  • CC[C@@H]1CN2CC[C@@]3(O)C(=Nc4cccc(OC)c34)[C@@H]2C[C@@H]1\C(=C/OC)C(=O)OC
  • CC[C@@H]1CN2CC[C@@]3(O)C(=NC4=CC=CC(OC)=C34)[C@@H]2C[C@@H]1\C(=C/OC)C(=O)OC
Properties
C23H30N2O5
Molar mass 414.502 g·mol−1
log P 1.266
Acidity (pKa) 12.203
Basicity (pKb) 1.794
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

Metabolism

After a kratom study, it was revealed that 7-OH converts into mitragynine pseudoindoxyl.[8][9] Interestingly, this even more potent opioid was revealed to exist in a mixture of stereoisomers in biological systems.[10]

Mitragynine Pseudoindoxyl
Mitragyna speciosa alkaloids at opioid receptors
CompoundAffinities (KiTooltip Inhibitor constant)RatioRef
MORTooltip μ-Opioid receptorDORTooltip δ-Opioid receptorKORTooltip κ-Opioid receptorMOR:DOR:KOR
7-Hydroxymitragynine13.51551231:11:9[11]
Mitragynine7.2460.31,1001:8:152[11]
Mitragynine pseudoindoxyl0.0873.0279.41:35:913[11]

Pharmacology

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.[12][13] It also acts on alpha 2 adrenergic and 5-HT2A receptors.[13] 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.[12]

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.[12]

See also

References
  1. Chemical Abstracts Service: Columbus, OH, 2004; RN 174418-82-7 (accessed via SciFinder Scholar, version 2007.3; November 30, 2011)
  2. Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-15.
  3. 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.
  4. 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.
  5. "7-Hydroxymitragynine - Green Leaf Kratom - Kratom Blogs Archives". Green Leaf Kratom. 2020-08-19. Retrieved 2020-08-22.
  6. 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.
  7. Spetea M, Schmidhammer H (June 2019). "Unveiling 7-Hydroxymitragynine as the Key Active Metabolite of Mitragynine and the Promise for Creating Novel Pain Relievers". ACS Central Science. 5 (6): 936–938. doi:10.1021/acscentsci.9b00462. PMC 6598155. PMID 31263752.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.

Further reading
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