Centrally acting non-narcotic antitussives prevent hyperactivity in mice: Involvement of GIRK channels

Pharmacology, Biochemistry, and Behavior
Fumio SoedaKazuo Takahama

Abstract

We have previously reported that centrally acting non-narcotic antitussives inhibited G protein-coupled inwardly rectifying potassium (GIRK) channel-activated currents, and that the antitussives had multiple pharmacological actions on various models of intractable brain diseases in rodents. In this study, the question of whether these antitussives inhibit drug-induced hyperactivity in mice was investigated. Antitussives, such as cloperastine and tipepidine, at cough suppressant doses, inhibited an increase in ambulation of mice neonatally treated with 6-hydroxydopamine. In addition, all antitussives studied inhibited an increase in methamphetamine-induced hyperactivity in mice. Methylphenidate, which is used for treatment of ADHD, inhibited 6-hydroxydopamine-lesion-induced, but not methamphetamine-induced, hyperactivity in mice. By the rota-rod test, the drugs had little effect on motor coordination of the hyperactive mice. Significant correlation was found between the ameliorating effects of antitussives on methamphetamine-induced hyperactivity and their inhibitory actions on GIRK channel currents (coefficient factor, 0.998). Furthermore, tertiapin, a GIRK channel blocker, prevented an increase in methamphetamine-induced hyper...Continue Reading

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Citations

May 18, 2019·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Georg C ZieglerKlaus-Peter Lesch
Sep 18, 2020·Expert Opinion on Emerging Drugs·Marco PozziMaria Nobile
Nov 5, 2020·Expert Opinion on Emerging Drugs·Ann C ChildressMargaret D Weiss
Jan 21, 2021·Trends in Pharmacological Sciences·Yulin ZhaoPaul A Slesinger
Jun 26, 2021·Pediatrics International : Official Journal of the Japan Pediatric Society·Tomohito HayakawaAkihisa Okumura

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