Neuroprotective effects of a dual L/N-type Ca(2+) channel blocker cilnidipine in the rat focal brain ischemia model.
Although a blockade or lack of N-type Ca(2+) channels has been reported to suppress neuronal pathological processes in several animal models of pain and ischemic brain injury, information is still limited regarding the neuroprotective effects of a dual L/N-type Ca(2+) channel blocker, cilnidipine. In this study, we assessed the effects of cilnidipine in the rat focal brain ischemia model to analyze its potential utility for hypertensive patients with cerebral infarction. In an anesthetized rat model, cerebral vasodilator actions of cilnidipine were detected at hypotensive doses, which was less potent than those of an L-type Ca(2+) channel blocker, nilvadipine. In the rat focal brain ischemia model, an anti-hypertensive and anti-sympathetic dose of cilnidipine could reduce the size of cerebral infarction, whereas an equipotent hypotensive dose of nilvadipine failed to affect it. These results suggest that N-type Ca(2+) channel-blocking profile of cilnidipine may contribute its neuroprotective action in the animal focal brain ischemia model. Thus, treatment of hypertension with cilnidipine may prevent severe consequences after brain attack.
Takahara
Akira
A
Pharmaceutical Research Laboratories, Pharmaceuticals Company, Ajinomoto Co. Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawaski 210-8681, Japan. akirat@yamanashi.ac.jp
Konda
Tomoyuki
T
Enomoto
Azusa
A
Kondo
Nobuo
N
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020864:Calcium Channels, N-Type / Q000187:drug effects; D002544:Cerebral Infarction / Q000188:drug therapy; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; C035100:nilvadipine; C065927:cilnidipine; D009543:Nifedipine