DY-9760e, a calmodulin antagonist, reduces brain damage after permanent focal cerebral ischemia in cats |
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Authors: | Sugimura Masunobu Takamori Hideo Fukushi Hiromichi Kitano Yutaka Kanazawa Yoshito Shirasaki Yasufumi |
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Institution: | New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. shiram8s@daiichipharm.co.jp |
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Abstract: | DY-9760e (3-2-4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate), a calmodulin antagonist, provides protection against Ca(2+) overload-associated cytotoxicity and brain injury after cerebral ischemia in rats. In this study, we assessed the effect of DY-9760e on ischemic infarct volume in cats subjected to permanent focal cerebral ischemia. DY-9760e was infused for 6 h, beginning 5 min after occlusion of the middle cerebral artery. The infarct volume was measured at the end of drug infusion. DY-9760e, at the dose of 0.25 but not 0.1 mg/kg/h, significantly reduced cerebral infarct volume without affecting any physiological parameters, and its protective effect was mainly evident in the cerebral cortex, where the penumbra, a salvageable zone, exists. The present study demonstrates that DY-9760e protects against brain injury after focal ischemia in a gyrencephalic animal as well as in the rodents reported previously and suggests its therapeutic value for the treatment of acute stroke. |
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