Chemistry:7-Hydroxymitragynine

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Short description: Alkaloid analgesic compound
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
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).
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Infobox references

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 the mitragynine present in the kratom leaf. 7-OH binds to opioid receptors like mitragynine, but research suggests that 7-OH binds with greater potency.[4]

7-Acetoxymitragynine

Dependence and withdrawal

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.[5][6] It also acts on alpha 2 adrenergic and 5-HT2A receptors.[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

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

Mitragynine Pseudoindoxyl
Mitragyna speciosa alkaloids at opioid receptors
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

References

  1. ↑ 1.0 1.1 Chemical Abstracts Service: Columbus, OH, 2004; RN 174418-82-7 (accessed via SciFinder Scholar, version 2007.3; November 30, 2011)
  2. ↑ "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. March 2004. doi:10.1016/j.lfs.2003.09.054. PMID 14969718. 
  3. ↑ "A New Indole Alkaloid, 7 alpha-Hydroxy-7H-mitragynine, from Mitragyna speciosa in Thailand". Planta Medica 60 (6): 580–581. December 1994. doi:10.1055/s-2006-959578. PMID 17236085. 
  4. ↑ "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. May 2018. doi:10.1016/j.neuropharm.2017.08.026. PMID 28830758. 
  5. ↑ 5.0 5.1 5.2 "Kratom-Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review". Pain and Therapy 9 (1): 55–69. June 2020. doi:10.1007/s40122-020-00151-x. PMID 31994019. 
  6. ↑ 6.0 6.1 "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. 2017. doi:10.36076/ppj.2017.1.E195. PMID 28072812. 
  7. ↑ "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. September 2016. doi:10.1021/acs.jmedchem.6b00748. PMID 27556704. 
  8. ↑ "Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy". ACS Pharmacology & Translational Science 3 (6): 1063–1068. December 2020. doi:10.1021/acsptsci.0c00075. PMID 33344889. 
  9. ↑ "Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy". ACS Pharmacology & Translational Science 3 (6): 1063–1068. December 2020. doi:10.1021/acsptsci.0c00075. PMID 33344889. 
  10. ↑ 10.0 10.1 10.2 "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. April 2002. doi:10.1021/jm010576e. PMID 11960505. 

Further reading

  • "Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa". Chemical & Pharmaceutical Bulletin 52 (8): 916–928. August 2004. doi:10.1248/cpb.52.916. PMID 15304982. 



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