7-hydroxymitragynine (7-OH) is a minor alkaloid compound found in the plant Mitragynia speciosa (also known as kratom).1 Although it is a minor alkaloid in terms of quantity, 7-OH is very interesting to scientists because of its potency and analgesic effects.
The Chemistry of 7-Hydroxymitragynine
7-OH is the oxidized derivative of mitragynine, the primary alkaloid in kratom.
Studies exploring the total and partial synthesis of 7-OH (and its parent compound mitragynine) reveal some interesting findings regarding the structure-activity relationship (SAR) of their molecular scaffold and its interaction with mu opioid receptors (MOR).2–7 For example, the MOR activity of 7-OH stops when small molecular changes are made to the acrylate and ethyl groups on one of the rings. Also, the demethylation of the aryl methoxy group reduces the potency of 7-OH at the MOR.
The Pharmacology of 7-Hydroxymitragynine
Studies have been done to examine how 7-OH interacts with the human mu opioid receptors (hMORs).4 Combining docking study observations with what is known about the SAR of 7-OH at hMORs, suggests that 7-OH and its structural analogs adopt a distinct binding pose in the receptor pocket. Additional experiments showed that 7-OH had a Ki value of 47 nM and was a partial agonist at hMOR.
In addition, studies have shown that 7-OH acts as a competitive antagonist at the human kappa (hKOR) and delta (hDOR) opioid receptors.4
Data from a 2014 study indicates that 7-OH has sufficient permeability and efflux ratios to pass through the blood-brain barrier via passive diffusion.8
The Applications and Potential of 7-Hydroxymitragynine
Research indicates that the analgesic effects of 7-OH are due to its agonist behavior at hMOR. In mice, 7-OH has a potency at hMOR that is 4- to 5-fold higher than the opioid agonist morphine when administered subcutaneously.9,10 Via the oral route, 7-OH is 10- to 20-fold more potent than morphine (morphine has poor oral bioavailability).11 But because it is only a partial agonist, 7-OH has side effects that are significantly milder than morphine.12
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