Beneficial effect of OKY-046, a selective thromboxane A2 synthetase inhibitor, on experimental cerebral vasospasm

Japanese Journal of Pharmacology
H KomatsuS Hiraku

Abstract

Effects of OKY-046, a selective inhibitor of thromboxane (TX)A2 synthetase and a platelet aggregation inhibitor, on in vitro and in vivo models of cerebral vasospasm were studied. The contraction of the isolated rabbit basilar artery by an exposure to 1.0 ml of whole rabbit blood plus 0.05 or 0.1 units/ml of thrombin was diminished by the treatment with 10(-4) M of OKY-046 and/or 10(-6) M of cinanserin. When the whole blood of rabbits treated intravenously with 1 mg/kg/min of OKY-046 was used, the contraction of the basilar artery was decreased to about half of the control contraction. Angiographically recognized cerebral vasospasm in vivo, by a transorbital injection of 5.0 to 7.0 ml of autologous arterial blood into the cisterna magna of dogs, was suppressed by 0.05 and 0.5 microgram of OKY-046. Moreover, the decrease in the regional cerebral blood flow in autologous blood infused-dogs was inhibited by 0.5 microgram of OKY-046. The increase in TXB2 in the cerebrospinal fluid of dogs was significantly inhibited, and the level of 6-keto-PGF1 alpha was slightly increased by the treatment of OKY-046. The ratio of 6-keto-PGF1 alpha/TXB2 was increased from 1.5 to 5.2 in OKY-046-treated dogs. No effect on the basal tone and response...Continue Reading

Citations

Jan 29, 2011·Journal of Biomedicine & Biotechnology·Sang In ParkKyung-Sool Jang
Jul 14, 2000·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·K I KawanoK Umemura
Feb 1, 1989·Stroke; a Journal of Cerebral Circulation·B B ChehraziR M Joy
Apr 16, 2011·The Journal of Pharmacology and Experimental Therapeutics·Akihiro KoumuraHideaki Hara

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