期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 144, 期 -, 页码 26-32出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2016.02.006
关键词
Methamphetamine; 6-OHDA; GIRK channel; Hyperactivity; Antitussives; ADHD
资金
- MEXT KAKENHI [16659066, 17790101]
- Grants-in-Aid for Scientific Research [17790101, 16659066] Funding Source: KAKEN
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-hydroxydopaminelesion-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. (C) 2016 Elsevier Inc. All rights reserved.
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