In vitro stability and metabolism of salvinorin A in rat  plasma.
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.
Tsujikawa
K
K
National Research Institute of Police Science, Kashiwa, Japan. tujikawa@nrips.go.jp
Kuwayama
K
K
Miyaguchi
H
H
Kanamori
T
T
Iwata
Y T
YT
Inoue
H
H
D000818:Animals; D004224:Diterpenes / Q000097:blood / Q000493:pharmacokinetics*; D045785:Diterpenes, Clerodane / Q000097:blood / Q000493:pharmacokinetics*; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004950:Esterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006213:Hallucinogens / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D027544:Salvia / Q000737:chemistry
D004224:Diterpenes; D045785:Diterpenes, Clerodane; D004791:Enzyme Inhibitors; D006213:Hallucinogens; C508456:salvinorin B; D004950:Esterases; C090499:salvinorin A