OPC-21268, an orally effective, nonpeptide arginine vasopressin V1 receptor antagonist reduces vasogenic brain edema

Acta Neurochirurgica. Supplement
I BemanaS Nagao

Abstract

We examined the effect of orally administered OPC-21268, a nonpeptide Arginine Vasopressin V1 receptor antagonist, on cold induced vasogenic brain edema in rat. Cold brain injury was induced by applying a copper rode cooled with liquid nitrogen for one minute. To mimic clinical use, one hour after induction of the cold lesion, rats were treated with orally administered OPC-21268 at doses of 100 mg, 200 mg, and 300 mg/kg every 8 hr for 24 hours. Two percent Evans blue in saline, in a volume of 1 ml/kg was given intravenously prior to cold injury. Twenty four hours after induction the cold lesion, brain water, brain tissue electrolytes, and plasma osmolality and electrolytes were measured. Quantitative evaluation of BBB permeability was performed using the Evans blue fluorescence method. The injury resulted in significant increases in the brain water and brain tissue sodium, and Evans blue concentration in both the lesioned and contralateral hemispheres (p < 0.01). OPC-21268 at doses of 200 mg and 300 mg/kg significantly decreased brain water and Evans blue concentrations in both the lesioned and contralateral hemispheres (p < 0.01). Brain tissue sodium content was significantly reduced at a dose of 300 mg/kg in the lesioned side...Continue Reading

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