7-Hydroxymitragynine

In this article we are going to explore 7-Hydroxymitragynine, a topic that has captured the attention of many over the years. From its origins to its impact on modern society, 7-Hydroxymitragynine has been the subject of debate and discussion. As we delve deeper into this topic, we will discover its implications in different areas, as well as the advances and challenges that surround it. Using a critical and analytical approach, we will examine the importance of 7-Hydroxymitragynine in today's world and how it has shaped our perception and understanding of it. Through this article, we hope to offer a deeper and more complete vision of 7-Hydroxymitragynine, inviting our readers to reflect on its relevance and meaning today.

7-Hydroxymitragynine
Clinical data
Other names7α-Hydroxy-7H-mitragynine;[1] 9-Methoxycorynantheidine hydroxyindolenine[1]
Routes of
administration		By mouth
Drug classOpioid
ATC code
  • None
Legal status
Legal status
  • BR: Class F1 (Prohibited narcotics)
  • US: Unscheduled
Pharmacokinetic data
MetabolitesMitragynine pseudoindoxyl
Identifiers
  • Methyl (2E)-2-quinolizin-2-yl]-3-methoxyprop-2-enoate
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H30N2O5
Molar mass414.502 g·mol−1
3D model (JSmol)
  • CC1CN2CC3(O)C(=Nc4cccc(OC)c34)2C1\C(=C/OC)C(=O)OC

  • CC1CN2CC3(O)C(=NC4=CC=CC(OC)=C34)2C1\C(=C/OC)C(=O)OC
  • 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

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

Main article: Mitragynine § 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] 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

7-Hydroxymitragynine can convert into mitragynine up to 45% in human liver microsomes over a 2 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]

Mitragynine Pseudoindoxyl
Mitragyna speciosa alkaloids at opioid receptors
Compound Affinities (KiTooltip Inhibitor constant) Ratio Ref
MORTooltip μ-Opioid receptor DORTooltip δ-Opioid receptor KORTooltip κ-Opioid receptor 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. ^ a b Chemical Abstracts Service: Columbus, OH, 2004; RN 174418-82-7 (accessed via SciFinder Scholar, version 2007.3; November 30, 2011)
  2. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  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. ^ 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.
  10. ^ 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