In vitro stability and metabolism of salvinorin A in rat plasma.
K Tsujikawa, K Kuwayama, H Miyaguchi, T Kanamori, Y T Iwata, H Inoue
Xenobiotica; the fate of foreign compounds in biological systems May 1, 2009 DOI: 10.1080/00498250902769967 via PubMed
Summary
AI-generated from the abstractSalvinorin A, the main psychoactive compound in Salvia divinorum, breaks down rapidly in rat plasma. At 37 degrees Celsius, its degradation rate constant was 3.8 x 10^(-1) per hour, much faster than at 4 degrees Celsius, where it was less than 6.0 x 10^(-3) per hour. The enzyme carboxylesterase primarily drives this breakdown, as inhibitors of that enzyme strongly suppressed degradation, while inhibitors of other esterases had little effect. The degradation products include salvinorin B (the deacetylated form) and lactone-ring-open forms of both salvinorin A and salvinorin B, with the ring-opening reactions involving a calcium-dependent lactonase.
Study at a glance
| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rat plasma |
| Topics | Salvia divinorum |
| Keywords | Potent natural compound This compound Drug metabolism Break down |
| Citations | 64 |
| Key finding | Carboxylesterase is the main enzyme responsible for salvinorin A hydrolysis in rat plasma, producing salvinorin B and lactone-ring-open forms. |
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.