Bio-receptor Screening and MAO Inhibition
(This site is created and maintained by Daniel Siebert)

In 1993, I sent a sample of salvinorin-A to Dave Nichols at Purdue University. Dr. Nichols was involved in an NIMH funded research program, which enabled him to have the material exhaustively screened by the commercial bio-receptor screening service, NovaScreen™.

The screening results showed no significant competitive inhibition of reference target compounds at any of the following sites tested. The receptor sites tested included those effected by most other major psychoactive drugs.

Many years later, in 2001, I sent a sample to Bryan Roth, project director of the NIMH Psychoactive Drug Screening Program. Dr. Roth’s group tested the compound for binding affinity at more than fifty receptors, transporters, and ion-channels. Although many of these molecular targets had been checked previously in the NovaScreen assays performed for Dr. Nichols, this study differed in that it mainly used human-cloned, rather than animal, receptors. The results confirmed those of the previous study, as the compound showed no significant activity at any of the previously tested sites. Salvinorin A did, however, prove to be highly active at one of the newly tested receptors: the kappa-opioid receptor. It showed no significant activity at other opioid receptor types. Using functional assays, it was determined that salvinorin A is an extraordinarily potent and highly selective kappa-opioid receptor agonist. This discovery revealed, for the first time, a fundamental aspect of this compound’s mechanism of action, and as such, it represents a major landmark in the history of Salvia divinorum. In 2002 Roth’s group published these findings together with a preliminary model of the molecular mechanisms by which salvinorin A might bind to the kappa-opioid receptor. Click here to access that paper.