Some central pharmacological effects of the calcium channel antagonist flunarizine.
Our earlier studies showed that dihydropyridine calcium channel antagonists have some central pharmacological effects. Flunarizine is considered to be a calcium channel antagonist; therefore this study was aimed at investigating the effect of flunarizine (given in single doses of 5, 10 and 20 mg/kg p.o.) in behavioural models in which calcium channel antagonists of the dihydropyridine type were previously studied. Flunarizine inhibited the apomorphine-induced stereotypy and yawning behaviour in rats. It decreased the hypothermia induced by a low dose of apomorphine in mice, but not that one induced by high dose of it. The quinpirole-induced hypothermia was also reduced. In the tests used for evaluation of the effect on the serotonergic system, flunarizine decreased the 5-HTP-induced head twitches and partly antagonized the fenfluramine- and quipazine-induced hyperthermias (at a high ambient temperature). In the forced swimming test flunarizine was inactive in mice and rats. The obtained results indicate that flunarizine exerts central antagonistic effects on the dopaminergic and serotonergic systems and has no antidepressant activity. Flunarizine differs from calcium channel antagonists of the dihydropyridine type, which have no dopamine-antagonistic activity and show anti-depressant-like properties.
Czyrak
A
A
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Mogilnicka
E
E
Maj
J
J
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists; D004347:Drug Interactions; D004873:Ergolines / Q000494:pharmacology; D005277:Fenfluramine / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013045:Species Specificity; D013239:Stereotyped Behavior / Q000187:drug effects*; D015000:Yawning / Q000187:drug effects*
D018492:Dopamine Antagonists; D004873:Ergolines; D012702:Serotonin Antagonists; D019257:Quinpirole; D005277:Fenfluramine; D012701:Serotonin; D011814:Quipazine; D006916:5-Hydroxytryptophan; D001058:Apomorphine; D005444:Flunarizine; D004298:Dopamine