Peculiar effects of isradipine and darodipine on the rat brain dopaminergic system.
1. Darodipine and isradipine are dihydropyridine calcium antagonists which easily cross the blood-brain barrier displaying high affinity and specificity for the brain "L" type voltage-sensitive calcium channel. In rat striatum and fronto-parietal cortex the effects of i.p. administration of these drugs on the dopaminergic system were evaluated. 2. Both drugs showed neuroleptic-like activity on spontaneous motility at a dose of 5 mg/kg or more. 3. Isradipine, being almost ineffective in the frontoparietal cortex, affected the striatal DA turnover. On the contrary, darodipine affected the DA turnover of the frontoparietal cortex, being almost ineffective in the striatum. 4. Both drugs, unlike nimodipine, appeared to display their antidopaminergic effects by enhancing the intraneuronal DA metabolism. 5. It was concluded that the antidopaminergic properties of isradipine and darodipine are characterized by their regional specificity and a peculiar profile of actions. However, these drugs (as well as nimodipine and other calcium antagonists) show neuroleptic-like effects at doses which should markedly affect the cardiovascular system.
Gaggi
R
R
Department of Pharmacology, University of Bologna, Italy.
Dall'Olio
R
R
Roncada
P
P
Gianni
A M
AM
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D017275:Isradipine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D010296:Parietal Lobe / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D015102:3,4-Dihydroxyphenylacetic Acid; D009553:Nimodipine; D009543:Nifedipine; D006220:Haloperidol; C034600:darodipine; D004298:Dopamine; D006719:Homovanillic Acid; D017275:Isradipine