In vitro stability and metabolism of salvinorin A in rat plasma.
Kenji Tsujikawa, Kenji Kuwayama, Hajime Miyaguchi, Tatsuyuki Kanamori, Yuko T Iwata, H Inoue
Xenobiotica; the fate of foreign compounds in biological systems May 1, 2009 DOI: 10.1080/00498250902769967 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rat plasma |
| Topics | Salvia divinorum |
| Keywords | Potent natural compound This compound Drug metabolism Break down Rapid degradation Efficiently metabolizes Enzymes Carboxylesterase Lactonase Key players Salvinorin b Distinct breakdown products Pharmacokinetics Pharmacology Stability in plasma |
| Citations | 64 |
| Key findings | 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.