The effects of two 21-aminosteroids on overt infarct size 48 hours after middle cerebral artery occlusion in the rat.
The lipid peroxidation inhibitors U74006F (21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9]-(11)-triene-3, 20-dione) and U74512E (21-[4-(3-ethylamino-2-pyridinyl)-1-piperazinyl]-16 alpha-methylpregna- 1,4,9]-(11)-triene-3,20-dione) were tested for cerebroprotective properties in the rat. Focal cerebral ischemia was induced by irreversible occlusion of the middle cerebral artery (MCA-O). The 21-aminosteroids U74006F (1 mg/kg or 10 mg/kg, i.p.) and U75412E (1 mg/kg or 30 mg/kg, i.p.) were injected 30 min prior and 2, 6, and 24 h after MCA-O. The higher doses of U74006F or U75412E caused reductions in cortical infarct size ranging from 28 to 34%. The data suggest the 21-aminosteroids to be mildly effective after irreversible occlusion of the MCA but possibly to be more beneficial as part of a combined drug therapy in conjunction with Ca2+ or NMDA antagonists.
Beck
T
T
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York.
Bielenberg
G W
GW
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications*; D002544:Cerebral Infarction / Q000209:etiology* / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013256:Steroids / Q000494:pharmacology*
D011281:Pregnatrienes; D013256:Steroids; C069980:U 75412E; C053355:tirilazad