Calcium antagonists for reduction of brain damage in stroke.
In a rat model of embolic stroke [permanent occlusion of the left middle cerebral artery (MCAO)], isradipine, a 1,4-dihydropyridine calcium antagonist, reduced the infarct size by more than 50%, as determined by both in vivo magnetic resonance imaging (MRI) and postmortem histology. Among several calcium antagonists tested, including nimodipine, nitrendipine, and nifedipine, isradipine was found to be the most potent and most efficacious. These results suggest that isradipine, when administered shortly after stroke onset, may have beneficial effects in patients suffering from brain ischemia. When high blood pressure in spontaneously hypertensive rats (SHR) was normalized by daily injections of isradipine, brain damage caused by a subsequent stroke (MCAO) was substantially reduced by as much as 75% in the cortex compared to controls. These results suggest that isradipine, when used as an antihypertensive drug in humans, may offer the additional benefit of reducing brain damage caused by an eventual stroke. Because high blood pressure is considered an important risk factor for stroke, this additional benefit of isradipine would be particularly valuable in antihypertensive therapy.
Central Nervous System Unit of Preclinical Research, Sandoz Ltd., Basel, Switzerland.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000473:pathology; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017275:Isradipine; D008279:Magnetic Resonance Imaging; D008297:Male; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
D002121:Calcium Channel Blockers; D011725:Pyridines; D017275:Isradipine