title: DY-9760e, a calmodulin antagonist, reduces brain damage after permanent focal cerebral ischemia in cats.
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.
authors.affiliation: New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. shiram8s@daiichipharm.co.jp
authors.forename: Masunobu
authors.initials: M
authors.lastname: Sugimura
authors.forename: Hideo
authors.initials: H
authors.lastname: Takamori
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Fukushi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kitano
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kanazawa
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Shirasaki
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000503:physiopathology; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D013687:Telencephalon / Q000473:pathology
chemical_list: C109602:3-(2-(4-(3-chloro-2-methylphenyl)1-piperazinyl)ethyl)5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazol dihydrochloride 3.5 hydrate; D002147:Calmodulin; D007191:Indazoles