Benzothiazepines, diltiazem and JTV-519, exert an anxiolytic-like effect via neurosteroid biosynthesis in mice

Kazumi Yoshizawa; Kozue Nakashima; Mizuho Tabuchi; Ayano Okumura; Yuko Nakatake; Mitsuhiko Yamada; Yayoi Tsuneoka; Tatsuya Higashi

Journal of Pharmacological Sciences (Jul 2020)

Benzothiazepines, diltiazem and JTV-519, exert an anxiolytic-like effect via neurosteroid biosynthesis in mice

Kazumi Yoshizawa,
Kozue Nakashima,
Mizuho Tabuchi,
Ayano Okumura,
Yuko Nakatake,
Mitsuhiko Yamada,
Yayoi Tsuneoka,
Tatsuya Higashi

Affiliations

Kazumi Yoshizawa: Laboratory of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan; Corresponding author. Laboratory of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Fax: +81 4 7121 3651.
Kozue Nakashima: Laboratory of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan
Mizuho Tabuchi: Laboratory of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan
Ayano Okumura: Laboratory of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan
Yuko Nakatake: Laboratory of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan; Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan
Mitsuhiko Yamada: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan
Yayoi Tsuneoka: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Japan
Tatsuya Higashi: Laboratory of Analytical and Bioanalytical Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan

Journal volume & issue: Vol. 143, no. 3
pp. 234 – 237

Abstract

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We investigated whether benzothiazepines could produce anxiolytic effects via allopregnanolone (ALLO) biosynthesis in mice. We compared the behavioral effects caused by benzothiazepines to those caused by carbamazepine and sodium valproate. We found that a pretreatment with finasteride (a 5 alpha-reductase inhibitor) suppressed carbamazepine-induced anxiolytic effects but not the effects of sodium valproate. Similar to carbamazepine, diltiazem and JTV-519 displayed anxiolytic effects that were suppressed by a pretreatment with finasteride. We clearly demonstrate that the benzothiazepines, diltiazem and JTV-519, exert an anxiolytic-like effect via ALLO biosynthesis in mice.

Published in Journal of Pharmacological Sciences

ISSN: 1347-8613 (Print)
Publisher: Elsevier
Country of publisher: Japan
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmacological-sciences

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