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.

journal_name

Biol Pharm Bull

authors

Sugimura M,Takamori H,Fukushi H,Kitano Y,Kanazawa Y,Shirasaki Y

doi

10.1248/bpb.28.629

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

629-33

issue

4

eissn

0918-6158

issn

1347-5215

pii

JST.JSTAGE/bpb/28.629

journal_volume

28

pub_type

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