Potentiation of L-dopa-induced behavioral excitement by histamine H1-receptor antagonists in mice

Jpn J Pharmacol. 1996 May;71(1):81-4. doi: 10.1254/jjp.71.81.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Chlorpheniramine / pharmacology
  • Dopamine Agonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Histamine H1 Antagonists / pharmacology*
  • Levodopa / pharmacology*
  • Male
  • Mice
  • Tripelennamine / pharmacology

Substances

  • Dopamine Agonists
  • Histamine H1 Antagonists
  • Tripelennamine
  • Chlorpheniramine
  • Levodopa