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

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 hyperactivity of mice. These results demonstrated that antitussive drugs (cloperastine, tipepidine and caramiphen) possessing inhibitory action on GIRK channels inhibit drug-induced hyperactivity in mice, suggesting that such antitussives may potentially be therapeutic for patients with ADHD.

• Authors: Fumio Soeda, Yoshiko Fujieda, Mizue Kinoshita, Tetsuya Shirasaki, Kazuo Takahama
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 144 Pg. 26-32 (May 2016) ISSN: 1873-5177 [Electronic] United States
• PMID: 26892760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antitussive Agents
• G Protein-Coupled Inwardly-Rectifying Potassium Channels

Topics

• Animals
• Antitussive Agents (pharmacology)
• Female
• G Protein-Coupled Inwardly-Rectifying Potassium Channels (physiology)
• Hyperkinesis (prevention & control)
• Male
• Mice
• Pregnancy