Effect of the calcium entry blocker NB-818 on cerebral blood flow after unilateral carotid occlusion in the Mongolian gerbil.
The effect of NB-818 on regional cerebral cortical blood flow (rCBF) during normal and ischemic periods was studied in Mongolian gerbils by means of hydrogen clearance methods, and that effect was compared with that of nimodipine. In normal animals, the rCBF increased dose-dependently, when NB-818 was tested. The increased rCBF showed a slow onset and long duration of action. When comparing the potency of increase in rCBF, the action of NB-818 (0.01-0.1 mg/kg i.p.) was more potent and longer lasting than that of nimodipine (0.01-0.1 mg/kg i.p.). Thus, the cerebral ischemia, produced by unilateral common carotid artery (CCA) occlusion, was studied. Before the unilateral CCA occlusion, the rCBF value was 41.4 +/- 0.27 ml/100 g of brain per min. The rCBF after unilateral CCA occlusion in gerbils was divided into three types as follows: rCBF values of above 30 ml/100 g of brain per min (type I), between 20 to 29 ml/100 g of brain per min (type II) and below 19 ml/100 g of brain per min (type III). In type I and II, NB-818 (0.01-0.1 mg/kg i.p.) significantly improved the reduced rCBF after the occlusion, and its effects continued throughout the experiments. In type II and III, supratentorial brain edema was observed 4.5 hr after the occlusion. The brain edema was significantly inhibited by NB-818 in the type II but not in the type III because the increased rCBF in type III with NB-818 was slight.(ABSTRACT TRUNCATED AT 250 WORDS)
Nishikibe
M
M
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004095:Dihydropyridines; D005260:Female; D005849:Gerbillinae; D007274:Injections, Intraperitoneal; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009553:Nimodipine; C048962:NPK 1886; D009543:Nifedipine