In vitro stability and metabolism of salvinorin A in rat plasma
In vitro stability and metabolism of salvinorin A in rat plasma
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DOI：
10.1080/00498250902769967
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发表时间：
2009-01-01
期刊：
影响因子：
1.8
通讯作者：
Inoue, H.
中科院分区：
文献类型：
--
作者：
Tsujikawa, K.;Kuwayama, K.;Inoue, H.
鼠尾草素A是墨西哥鼠尾草中的主要活性精神活性成分，近年来作为致幻剂被广泛使用。本研究的目的是研究大鼠血浆中鼠尾草素A的稳定性、负责其降解的酯酶以及降解产物的估计。鼠尾草素A在37 ℃、25 ℃和4 ℃下的表观一级速率常数分别为3.8 × 10-1、1.1 × 10-1和6.0 × 10-3 h-1。鼠尾草素A的降解显着抑制添加氟化钠，酯酶抑制剂。此外，苯甲基磺酰氟（丝氨酸酯酶抑制剂）和双-对-硝基苯磷酸盐（羧酸酯酶抑制剂）也抑制鼠尾草素A降解。相比之下，很少或没有抑制的降解被视为与5，5-二硫代双-2-硝基苯甲酸（芳基酯酶抑制剂），ethopropazine（丁酰胆碱酯酶抑制剂），和BW 284 c51（乙酰胆碱酯酶抑制剂）。这些结果表明，羧酸酯酶主要参与大鼠血浆中鼠尾草素A的水解。通过液相色谱-质谱法估计的鼠尾草素A的降解产物包括脱乙酰化形式（鼠尾草素B）以及鼠尾草素A和鼠尾草素B的内酯开环形式。这种内酯开环反应与钙依赖性内酯酶有关。
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 37C, 25C, and 4C were 3.8 10-1, 1.1 10-1, and 6.0 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-nitrophenyl phosphate (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. 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.