Ischemia-induced changes in brain levels of monoamines and their metabolites of mice and rats: some protective effects of naftidrofuryl.

Employing two types of brain ischemic animal models, an attempt was made to evaluate the protective effect of naftidrofuryl as the normalizing effect on the ischemia-induced changes in the brain levels of monoamines and metabolites. 1) During 2 min ligation of both left and right common carotid arteries of mice, dopamine (DA) content alone significantly decreased among three monoamines and four metabolites measured by a high performance liquid chromatography-electrochemical detection method. Pretreatment with naftidrofuryl oxalate (45 mg/kg, i.p.) was found to prevent the DA change, but the lower dose (15 mg/kg, i.p.) of the drug or any other drug tested individually (vinpocetine hydrochloride: 2 mg/kg, Ca hopantenate: 0.1 g/kg, citicoline: 0.1 g/kg, i.p.) had no such effect. 2) Infusion of carbon microsphere (500 particles/100 microliters of 20% dextran/1.5 min/rat) into the right internal carotid artery induced various degree of time-dependent changes in the behavior and also in the brain levels of monoamines and metabolites. Embolized rats which otherwise would survive for at least 6 d after infusion, were divided into the lightly-infarcted and severely-infarcted groups by grading the behavioral abnormality. Subsequent treatments with naftidrofuryl oxalate (15 mg/kg, i.p., twice daily, totally 4 times) which was begun 16 h after microsphere injection, was found to accelerate the recovery rate of brain dopamine level once decreased by the embolism though only in the lightly-infarcted group. The significance of the results obtained herein were discussed in relation to the clinical effectiveness of naftidrofuryl in human brain ischemic diseases.