Cerebroprotective action of a Na+/Ca2+ channel blocker NS-7. I. Effect on the cerebral infarction and edema at the acute stage of permanent middle cerebral artery occlusion in rats.
The effect of a novel Na+/Ca2+ channel blocker NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride] on the cerebral infarction, edema and brain energy metabolism was investigated in rats after permanent middle cerebral artery occlusion (MCAO). The infarction and brain water content were evaluated at 48 h and 24 h after MCAO, respectively. A single bolus injection of NS-7 (0.03125-0.25 mg/kg) immediately after MCAO produced a dose-dependent reduction in the infarct volume as well as edema both in the cerebral cortex and striatum. Glycerol (4 g/kg) also decreased water content both in the occluded and non-occluded brain, but it did not reduce the size of cerebral infarction. Unlike glycerol, NS-7 did not change the water content in non-occluded brain. Moreover, a significant protective action was still observed even when NS-7 was injected once at 12 h after occlusion. In addition, NS-7 significantly reversed the decrease in tissue ATP content observed at 3 h but not at 0.5 h after MCAO. These findings suggest that a Na+/Ca2+ channel blocker NS-7 protects cerebral tissues against ischemic insults by improving the disturbance of cerebral energy metabolism and suppressing the cerebral edema.
Aoki
Y
Y
Research Laboratories, Nippon Shinyaku Co. Ltd., Nishiohji Hachijo, Minami-ku, Kyoto 601-8550, Japan.
Tamura
M
M
Itoh
Y
Y
Ukai
Y
Y
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D003451:Cryoprotective Agents / Q000494:pharmacology; D005990:Glycerol / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers
C106144:4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride; D002121:Calcium Channel Blockers; D003451:Cryoprotective Agents; D018696:Neuroprotective Agents; D011743:Pyrimidines; D026941:Sodium Channel Blockers; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005990:Glycerol