Potentiation of L-Dopa-Induced Behavioral Excitement by Histamine H1-Receptor Antagonists in Mice.

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  • Sato Tomoaki
    Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University
  • Suemaru Katsuya
    Department of Hospital Pharmacy, Okayama University Medical School
  • Matsunaga Kazuhisa
    Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University
  • Hamaoka Sumiko
    Department of Hospital Pharmacy, Okayama University Medical School
  • Gomita Yutaka
    Department of Hospital Pharmacy, Okayama University Medical School
  • Oishi Ryozo
    Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University

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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.

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