Effect of Clentiazem (TA-3090) with Posttreatment on Neurologic and Histologic Disorders of Stroke-Prone Spontaneously Hypertensive Rats with History of Stroke

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Abstract
Summary After stroke-prone spontaneously hypertensive rats (SHRSP) received a salt-loaded diet to accelerate onset of stroke, the therapeutic effect of clentiazem, a benzothiazepine Ca antagonist, on neurologic and histologic disorders was examined. Treatment with clentiazem (3, 15, and 30 mg/kg) orally twice daily (b.i.d.) for 28 days after the occurrence of stroke reduced neurologic symptoms and histologic changes of brain and kidney in a dose-dependent manner. Acute treatment with clentiazem (15 mg/kg, b.i.d.) administered immediately after stroke for 1 week not only almost completely abolished neurologic symptoms during treatment, but partially improved them even after treatment. Subacute treatment with clentiazem starting 10 days after stroke and continuing for 18 days also suppressed the neurologic signs. Both acute and subacute treatment improved cerebral histology. These results suggest that clentiazem treatment in the acute and subacute phases of stroke is beneficial After stroke-prone spontaneously hypertensive rats (SHRSP) received a salt-loaded diet to accelerate onset of stroke, the therapeutic effect of clentiazem, a benzothiazepine Ca antagonist, on neurologic and histologic disorders was examined. Treatment with clentiazem (3, 15, and 30 mg/kg) orally twice daily (b.i.d.) for 28 days after the occurrence of stroke reduced neurologic symptoms and histologic changes of brain and kidney in a dose-dependent manner. Acute treatment with clentiazem (15 mg/kg, b.i.d.) administered immediately after stroke for 1 week not only almost completely abolished neurologic symptoms during treatment, but partially improved them even after treatment. Subacute treatment with clentiazem starting 10 days after stroke and continuing for 18 days also suppressed the neurologic signs. Both acute and subacute treatment improved cerebral histology. These results suggest that clentiazem treatment in the acute and subacute phases of stroke is beneficial.

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