Pharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome
Pharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome
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DOI：
10.1021/acs.jnatprod.9b00600
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发表时间：
2019-11-01
影响因子：
5.1
通讯作者：
Arnold, Jonathon C.
中科院分区：
文献类型：
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作者：
Anderson, Lyndsey L.;Low, Ivan K.;Arnold, Jonathon C.
大麻产生许多生物活性分子的复杂混合物，包括被称为植物大麻素的萜烯酚化合物。植物大麻素以中性形式出现（例如，δ（9）-四氢大麻酚，THC;大麻二酚，CBD;等）或作为酸前体，其在植物中占优势（例如，δ（9）-四氢大麻酚酸，THCA;大麻二酚酸，CBDA;等）。人们对解锁植物大麻素酸的治疗应用越来越感兴趣;然而，目前对植物大麻素酸的基本药理学的理解是有限的。本文中，在小鼠中腹膜内施用后，检查CBDA、THCA、大麻环萜烯酸（CBCA）、大麻二伐那酸（CBDVA）、大麻萜酚酸（CBGA）和大麻萜伐那酸（CBGVA）的脑和血浆药代动力学曲线。接下来，在Dravet综合征小鼠模型（Scn 1a（RX/+）小鼠）中检查CBDA是否具有抗惊厥作用。所有研究的植物大麻素酸都被迅速吸收，血浆t（max）值在15至45分钟之间，半衰期相对较短（
Cannabis sativa produces a complex mixture of many bioactive molecules including terpenophenolic compounds known as phytocannabinoids. Phytocannabinoids come in neutral forms (e.g., Delta(9)-tetrahydrocannabinol, THC; cannabidiol, CBD; etc.) or as acid precursors, which are dominant in the plant (e.g., Delta(9)-tetrahydrocannabinolic acid, THCA; cannabidiolic acid, CBDA; etc.). There is increasing interest in unlocking the therapeutic applications of the phytocannabinoid acids; however, the present understanding of the basic pharmacology of phytocannabinoid acids is limited. Herein the brain and plasma pharmacokinetic profiles of CBDA, THCA, cannabichromenic acid (CBCA), cannabidivarinic acid (CBDVA), cannabigerolic acid (CBGA), and cannabigerovarinic acid (CBGVA) were examined following intraperitoneal administration in mice. Next it was examined whether CBDA was anticonvulsant in a mouse model of Dravet syndrome (Scn1a(RX/+) mice). All the phytocannabinoid acids investigated were rapidly absorbed with plasma t(max) values of between 15 and 45 min and had relatively short half-lives (