Effects of calcium antagonists nifedipine and flunarizine on phencyclidine-induced changes in the regional dopaminergic metabolism of the rat brain.
To elucidate the psychotropic actions of calcium (Ca) antagonists, we investigated the effect of the voltage-dependent Ca channel antagonists, nifedipine and flunarizine, on phencyclidine (PCP)-induced changes in the monoamine metabolism in the regional brain areas of rats. The results indicate that the administration of nifedipine alone attenuated dopamine (DA) metabolism in the nucleus caudatus putamen while enhancing serotonin (5-HT) metabolism. By contrast, flunarizine increased DA metabolism. PCP significantly increased DA metabolite levels in the prefrontal cortex, the nucleus caudatus putamen, and the amygdala. The PCP-induced increases in DA metabolism in these regions were significantly antagonized by nifedipine, but not by flunarizine. These results indicate that nifedipine attenuates the PCP-induced hyperactivity of the dopaminergic neurons, suggesting antipsychotic properties for this drug.
Etou
K
K
Department of Neuropsychiatry, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kuroki
T
T
Tatebayashi
Y
Y
Tashiro
N
N
Hirano
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005444:Flunarizine / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D006213:Hallucinogens; D015102:3,4-Dihydroxyphenylacetic Acid; D009543:Nifedipine; D010622:Phencyclidine; D005444:Flunarizine; D004298:Dopamine; D006719:Homovanillic Acid