Benzothiazepines, Diltiazem, and JTV-519 Exert Anxiolytic-Like Effects via Neurosteroid Biosynthesis in Mice

    March 2020 in “ Journal of Pharmacological Sciences ”
    Kazumi Yoshizawa, Kozue Nakashima, Mizuho Tabuchi, Ayano Okumura, Yuko Nakatake, Mitsuhiko Yamada, Yayoi Tsuneoka, Tatsuya Higashi
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    TLDR Benzothiazepines like diltiazem reduce anxiety in mice by making neurosteroids.
    The study from July 2020 demonstrated that benzothiazepines, including diltiazem and JTV-519, have anxiolytic-like effects in mice, which are mediated by the biosynthesis of neurosteroids. These effects were comparable to those of carbamazepine and were inhibited by finasteride, suggesting the involvement of neurosteroid biosynthesis. The study, which used a minimum of six mice per experimental replication, also indicated that sodium valproate operates through a different mechanism, as its effects were not suppressed by finasteride. While classical benzodiazepines act on GABAA receptors and the translocator protein (TSPO), benzothiazepines and benzoxazepines selectively target TSPO. The study did not measure the increase in the neurosteroid allopregnanolone (ALLO) levels but concluded that benzothiazepines could be potential treatments for anxiety related to cardiovascular disease due to their anxiolytic-like effects and the cardioprotective properties of JTV-519.
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