7-Hydroxymitragynine

7-Hydroxymitragynine (7-OH-MIT, often simply sold as 7-OH) is a terpenoid indole alkaloid present in the plant Mitragyna speciosa, commonly known as kratom.^[3] It was first described in 1994.^[4] In humans, it is produced as an active metabolite of mitragynine via hepatic oxidation.^[5] 7-OH-MIT exhibits greater binding affinity to μ-opioid receptors (MOR) than mitragynine.

7-Hydroxymitragynine

Clinical data
Other names	7-OH; 7α-Hydroxy-7H-mitragynine;[1] 9-Methoxycorynantheidine hydroxyindolenine[1]
Dependence liability	High
Addiction liability	High[2]
Routes of administration	By mouth; inhalation
Drug class	Opioid
ATC code	None
Legal status
Legal status	BR: Class F1 (Prohibited narcotics) US: Unscheduled
Pharmacokinetic data
Metabolites	Mitragynine pseudoindoxyl
Identifiers
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
CAS Number	174418-82-7 N
PubChem CID	44301524
ChemSpider	23152144 Y
UNII	2T3TWA75R0
ChEMBL	ChEMBL61630 Y
CompTox Dashboard (EPA)	DTXSID20903988
Chemical and physical data
Formula	C23H30N2O5
Molar mass	414.502 g·mol−1
3D model (JSmol)	Interactive image Interactive image
SMILES 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
InChI 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 Y Key:RYENLSMHLCNXJT-CYXFISRXSA-N Y

Pharmacology

7-OH-MIT, like mitragynine, appears to be a mixed opioid receptor agonist/antagonist, with recent research indicating that it acts as a partial agonist at μ-opioid receptors and as a competitive antagonist at δ- and κ-opioid receptors.^[6][7] Both 7-OH-MIT and mitragynine do not appear to activate the β-arrestin pathway, distinguishing it from traditional opiate and opioid chemicals.^[6] A study has found the binding affinity of 7-OH-MIT to be μ-opioid receptor (MOR) 37 (± 4) nM and δ-opioid receptor (DOR) 91 (± 8) nM and κ-opioid receptor (KOR) 132 (± 7) nM.^[8] Another study found the binding affinity of 7-OH-MIT to be MOR 16 (± 1) nM and DOR 137 (± 21) nM and KOR 133 (± 37) nM.^[9] Another study found the binding affinity of 7-OH-MIT to be MOR 13.5 nM, DOR 155 nM, and KOR 123 nM.^[10] Animal models have shown that 7-OH-MIT may produce physical dependence comparable to that of morphine. Cross-tolerance to morphine was evident in mice rendered tolerant to 7-hydroxymitragynine and vice versa. Naloxone-induced withdrawal signs were elicited equally in mice chronically treated with 7-hydroxymitragynine or morphine.^[11]

Synthesis

In natural kratom leaves, 7-hydroxymitragynine is only present in small amounts from 0.6%–0.7% on average.^{[citation needed]} Therefore, extracting 7-OH-MIT in high concentrations directly from natural kratom leaves is not practical. Instead, 7-hydroxymitragynine can be produced semisynthetically via the oxidation of mitragynine.^[5]