Tomoaki Sato (1), Katsuya Suemaru (2), Kazuhisa Matsunaga (1), Sumiko Hamaoka (2), Yutaka Gomita (2) and Ryozo Oishi (1,*)
(1) Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, Higashi-ku, Fukuoka 812-82, Japan (2) Department of Hospital Pharmacy, Okayama University Medical School, Okayama 700, Japan (*) To whom correspondence should be addressed.
Abstract: Effects of histamine H1-receptor antagonists on L-dopa-induced behavioral excitement were examined in mice to confirm behaviorally the inhibition of dopamine uptake by these compounds. L-Dopa (100 - 300 mg/kg, s.c.) combined with pargyline hydrochloride (80 mg/kg, i.p.) caused a dose-dependent behavioral excitement. The marked excitement induced by L-dopa (300 mg/kg) plus pargyline was significantly inhibited by pimozide (0.1 - 1 mg/kg, s.c.), a selective dopamine antagonist. Tripelennamine (10 mg/kg, s.c.), d-chlorpheniramine (1 and 2 mg/kg, s.c.), homochlorcyclizine (2 and 5 mg/kg, s.c.), diphenhydramine (2 and 5 mg/kg, s.c.) and mepyramine (2 and 5 mg/kg, s.c.) each markedly enhanced the moderate behavioral excitement induced by L-dopa (150 mg/kg) plus pargyline. These findings are behavioral evidence for inhibition of dopamine uptake by H1 antagonists, which has been suggested by neurochemical studies.
Keywords:
Histamine H1-receptor antagonist, Dopamine uptake, L-Dopa