In vitrostability and metabolism of salvinorin A in rat plasma

Abstract

Salvinorin A is the main active psychoactive ingredient in Salvia divinorum, a Mexican plant that has been widely available as a hallucinogen in recent years. The aims of this study were to investigate the stability of salvinorin A in rat plasma, esterases responsible for its degradation, and estimation of the degradation products. The apparent first-order rate constants of salvinorin A at 37 degrees C, 25 degrees C, and 4 degrees C were 3.8 x 10(-1), 1.1 x 10(-1), and < 6.0 x 10(-3) h(-1), respectively. Salvinorin A degradation was markedly inhibited by the addition of sodium fluoride, an esterase inhibitor. Moreover, phenylmethylsulfonyl fluoride (serine esterase inhibitor) and bis-p-nitrophenylphosphate (carboxylesterase inhibitor) also inhibited salvinorin A degradation. In contrast, little or no suppression of the degradation was seen with 5,5'-dithiobis-2-nitrobenzoic acid (arylesterase inhibitor),ethopropazine (butyrylcholinesterase inhibitor), and BW284c51 (acetylcholineseterase inhibitor). These findings indicated that carboxylesterase was mainly involved in the salvinorin A hydrolysis in rat plasma.4. The degradation products of salvinorin A estimated by liquid chromatography-mass spectrometry included the deacetylated form (salvinorin B) and the lactone-ring-open forms of salvinorin A and salvinorin B. This lactone-ring-opening reactions were involved in calcium-dependent lactonase.

Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

“…The first investigation dedicated to tracking the metabolism of salvinorin A in vitro was conducted by Tsujikawa et al (2009). By monitoring rat plasma samples, the contribution of several esterases relevant to human subjects could be monitored, including acetylcholinesterase, butyrylcholinesterase, arylesterase, and carboxylesterase.…”

Here Today, Gone Tomorrow…and Back Again? A Review of Herbal Marijuana Alternatives (K2, Spice), Synthetic Cathinones (Bath Salts), Kratom, Salvia divinorum, Methoxetamine, and Piperazines

“…Salvinorin A is degraded by several cytochrome oxidase isoenzymes, including CYP 2D6, CYP1A1, CYP2C18, and CYP2E1 [170]. One ex vivo study demonstrated that salvinorin A is hydrolyzed to an inactive metabolite, salvinorin B by blood esterases [171].…”

Determination of the unstable drug otilonium bromide in human plasma by LC–ESI-MS and its application to a pharmacokinetic study

“…4A), which implied that the plasma esterase was the main factor leading to the instability of OB. KF was suggested to be an effective plasma esterase inhibitor [12,13], which had been successfully used to solve the problem of instability of drugs in plasma [14][15][16]. Also, the method of immediately adding acetonitrile to freshly collected plasma could prevent the hydrolysis of drugs by esterase [17].…”