Potentiation of L-dopa-induced behavioral excitement by histamine H1-receptor antagonists in mice.
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.
Sato
T
T
Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Suemaru
K
K
Matsunaga
K
K
Hamaoka
S
S
Gomita
Y
Y
Oishi
R
R
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002744:Chlorpheniramine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051379:Mice; D014309:Tripelennamine / Q000494:pharmacology
D018491:Dopamine Agonists; D006634:Histamine H1 Antagonists; D014309:Tripelennamine; D002744:Chlorpheniramine; D007980:Levodopa