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: Masunobu Sugimura, Hideo Takamori, Hiromichi Fukushi, Yutaka Kitano, Yoshito Kanazawa, Yasufumi Shirasaki
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 28 Issue 4 Pg. 629-33 (Apr 2005) ISSN: 0918-6158 [Print] Japan
• PMID: 15802800 (Publication Type: Journal Article)

Chemical References

• 3-(2-(4-(3-chloro-2-methylphenyl)1-piperazinyl)ethyl)5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazol dihydrochloride 3.5 hydrate
• Calmodulin
• Indazoles

Topics

• Animals
• Brain Ischemia (drug therapy, physiopathology)
• Calmodulin (antagonists & inhibitors)
• Cats
• Dose-Response Relationship, Drug
• Hypoxia, Brain (drug therapy, physiopathology)
• Indazoles (pharmacology)
• Male
• Telencephalon (pathology)