DARK Classics in Chemical Neuroscience: Salvinorin A.
ACS chemical neuroscience – December 02, 2020
Source: PubMed
Summary
The unique `natural product` `salvinorin A`, derived from `Salvia divinorum`, stands out as the first non-alkaloidal `opioid` `hallucinogen`. Its distinct chemistry, interacting with the `kappa-opioid receptor`, leads to rapid, yet transient, effects. This discovery has profoundly influenced neuroscience, driving extensive research into novel synthetic compounds and showcasing its significant potential in drug development.
Abstract
Salvinorin A is the main bioactive compound in Salvia divinorum, an endemic plant with ancestral use by the inhabitants of the Mazateca mountain range (Sierra Mazateca) in Oaxaca, México. The main use of la pastora, as locally known, is in spiritual rites due to its extraordinary hallucinogenic effects. Being the first known nonalkaloidal opioid-mediated psychotropic molecule, salvinorin A set new research areas in neuroscience. The absence of a protonated amine group, common to all previously known opioids, results in a fast metabolism with the concomitant fast elimination and swift loss of activity. The worldwide spread and psychotropic effects of salvinorin A account for its misuse and classification as a drug of abuse. Consequently, salvinorin A and Salvia divinorum are now banned in many countries. Several synthetic efforts have been focused on the improvement of physicochemical and biological properties of salvinorin A: from total synthesis to hundreds of analogues. In this Review, we discuss the impact of salvinorin A in chemistry and neuroscience covering the historical relevance, isolation from natural sources, synthetic efforts, and pharmacological and safety profiles. Altogether, the chemistry behind and the taboo that encloses salvinorin A makes it one of the most exquisite naturally occurring drugs.