Effect of benidipine hydrochloride (KW-3049), on cerebral ischemia induced by bilateral occlusion of the common carotid arteries in rats.
The effect of benidipine on experimental cerebral ischemia was investigated in rats subjected to occlusion of the bilateral common carotid arteries. Benidipine (30 micrograms/kg, i.p.) improved neurological symptoms such as ataxia, convulsion and loss of righting reflex, and prolonged survival time after occlusion of the bilateral common carotid arteries. In the nicardipine (100 micrograms/kg, i.p.)-treated group, a similar effect was observed, whereas nifedipine (100, 300 micrograms/kg, i.p.) and verapamil (300 micrograms/kg, i.p.) did not show any beneficial effect in this model. Furthermore, pretreatment with benidipine (30 micrograms/kg, i.p.) suppressed the increase in cerebral water content 3 h after the occlusion. Nicardipine (100 micrograms/kg, i.p.) showed a tendency to reduce the increase in cerebral water content, though the effect was not statistically significant. Nifedipine (100 micrograms/kg, i.p.) produced no improvement. After occlusion of the bilateral common carotid arteries, depletion of adenosine triphosphate (ATP) and phosphocreatine (CP) and an accumulation of lactate occurred in a time-dependent manner. Prophylactic administration of benidipine (30 micrograms/kg, i.p.), 20 min before occlusion, attenuated the depletion of ATP and CP and the accumulation of lactate 3h after the occlusion. Furthermore, post-treatment with benidipine 30 min after occlusion also suppressed these metabolic disorders. In conclusion, the beneficial effects of benidipine in this severe cerebral ischemia model show that the compound has advantages over nicardipine, nifedipine and verapamil. Thus, these results suggest that benidipine may be useful in the treatment of acute ischemic cerebral damage.
Shirakura
S
S
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Karasawa
A
A
Kubo
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D017536:Carotid Artery, Common / Q000502:physiology*; D004095:Dihydropyridines / Q000627:therapeutic use*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009529:Nicardipine / Q000627:therapeutic use; D009543:Nifedipine / Q000627:therapeutic use; D010725:Phosphocreatine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007773:Lactates; D010725:Phosphocreatine; D019344:Lactic Acid; C061004:benidipine; D000255:Adenosine Triphosphate; D012964:Sodium; D014700:Verapamil; D009529:Nicardipine; D009543:Nifedipine; D011188:Potassium