Discriminative Stimulus Effects of Atypical Hallucinogen Salvinorin A, and Semi-Synthetic Analogs, Salvinorin B Methoxymethyl (MOM) and Salvinorin B Ethoxymethyl (EOM) Ethers

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Killinger, Bryan
thesis / dissertation description
Salvia divinorum, a small shrub belonging to the mint family, has been used for centuries by shamanic tribes as a psychedelic agent. The main active compound found in the Salvia divinorum plant is salvinorin A, a naturally occurring non-nitrogenous neoclerodane diterepene. Analogous compounds of salvinorin A, methyloxymethyl (MOM) and ethyloxymethyl (EOM) ethers, derived from a manipulation of the C2 acetyl position, show a greater affinity for the KOP site. The current investigation's prime objective was to use drug discrimination in male Sprague-Dawley rats to characterize the stimulus effects of salvinorin A and two synthetic derivatives of this compound in rats trained to discriminate kappa agonist, U69,593 (0.13mg/kg) from vehicle. The secondary objective was to use drug discrimination in male Sprague dawley rats to compare salvinorin A to typical hallucinogen lysergic acid diethylamide (LSD). Animals exhibited dose-dependent generalization to U69, 593 when test compounds salvinorin A (0.125-1.0mg/kg), salvinorin B EOM (0.01-0.03 mg/kg), and salvinorin B MOM (0.01-0.03 mg/kg) were administered. In contrast, salvinorin A failed to substitute in rats trained to discriminate LSD from vehicle.