Different effects of the calcium antagonists nimodipine and flunarizine on dopamine metabolism in the rat brain.
The effect of two calcium antagonists, nimodipine and flunarizine, on striatal dopamine (DA) metabolism in rats was compared. Flunarizine (5-20 mg/kg i.p.) caused a dose-dependent increase in the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus. Following the 20 mg/kg dose, DOPAC levels were maximally elevated by about 50% from 2 to 12 hrs after treatment. On the contrary, nimodipine at the dose of 20 mg/kg i.p. produced a modest decrease in DOPAC levels. Neither calcium antagonist modified DA content. However, both nimodipine and flunarizine, at the dose of 20 mg/kg, markedly reduced the accumulation of DOPAC in the caudate nucleus induced by haloperidol (1 mg/kg). It is suggested that flunarizine, but not nimodipine, has a neuroleptic-like action, whereas the two calcium antagonists have in common the ability to attenuate the hyperactivity of DA neurons.
Fadda
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Institute of Physiology, University of Cagliari, Italy.
Gessa
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GL
Mosca
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Stefanini
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D015102:3,4-Dihydroxyphenylacetic Acid; D009553:Nimodipine; D006220:Haloperidol; D005444:Flunarizine; D004298:Dopamine