Effects of antihistaminics on locomotor activity in mice. Comparison with opiate and amphetamine-induced hyperactivity.
1. Three histamine H1-receptor antagonists (tripelennamine, diphenhydramine and cyclizine) and two H2-receptor antagonists (ranitidine and cimetidine)--1 and 10 mg/kg--were tested alone or in combination with the opioid partial agonist buprenorphine (1 mg/kg), the opioid antagonist naloxone (1 mg/kg) or dextroamphetamine (3 mg/kg) on locomotor activity in mice. 2. All three H1-antihistaminics tested and the H2-antihistaminic, cimetidine, enhance locomotor activity in a dose-dependent manner. 3. Furthermore, tripelennamine, diphenhydramine, cyclizine, ranitidine and cimetidine potentiate the buprenorphine-induced hyperactivity. 4. Previous administration of naloxone blocks the tripelennamine- and diphenhydramine-induced hyperactivity. 5. On the other hand, none of antihistaminics tested modifies the amphetamine-induced locomotor stimulation. 6. These results suggest that H1- and H2-receptor antagonists effects on locomotor behavior in mice may be related with opioid mechanisms, but not with amphetamine mechanisms.
Leza
J C
JC
Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Lizasoain
I
I
Lorenzo
P
P
D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006633:Histamine Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology*
D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D009294:Narcotics; D002047:Buprenorphine; D003913:Dextroamphetamine