Kratom Derivatives

I found another kratom paper discussing the synthesis of compounds derived from mitragynine and their effects in mice. From the paper:

The oxidative derivatives of mitragynine, i.e., mitragynine pseudoindoxyl and 7-hydroxymitragynine, were found as opioid agonists with higher potency than morphine in the experiment with guinea pig ileum.

[7-hydroxymitragynine], a minor constituent of M. speciosa [kratom], was found to exhibit high potency to opioid receptors: about 13- and 46-fold higher than those of [mitragynine pseudoindoxyl] and [mitragynine], respectively.

The intrinsic activity of [7-hydroxymitragynine] suggested its full agonistic property on opioid receptors.

In other words, the main active alkaloid of kratom is a full agonist (activator) of μ-opioid receptors and is quite potent. Furthermore:

It was also found that the methoxy group on the indole ring at the C9 position as well as the Nb lone electron pair in the fundamental structure of Corynanthe type indole alkaloid are essential structural functions for opioid agonistic activity. With altering the functional group at the C9 position, i.e., OMe -> OH -> H, of mitragynine, the activities of compounds dramatically shifted from that of full agonists through partial agonists to that of antagonists on opioid receptors.

So it's relatively easy to modify mitragynine to be a full agonist, partial agonist, or antagonist. The medical implications for this could be huge, with designer pharmaceuticals with just the correct proportions of each of these to provide effective pain relief while also preventing a tolerance buildup. This also explains the antagonistic properties of kratom; the process they did of OMe -> OH -> H is the opposite of the process the plant uses to synthesis mitragynine. So these intermediates are present in the leaf, most likely being responsible for kratom also being an opioid antagonist as well as an agonist.

The full text of the paper can be found here on Scribd. There is also a link to download the PDF on there.