Effects of nimodipine on biogenic amines in discrete brain areas

Discrete brain sections were obtained from rats after once or repeatedly given intraperitoneal nimodipine at doses ranging from 2.5 to 40 mg/kg. The single or the last treatment was carried out at 2-8 h before killing. The biogenic amine and metabolite content of the tissue samples were determined by high-performance liquid chromatography with electrochemical detection. The nimodipine-induced effects, chiefly regarding the brainstem, the thalamus-midbrain and the striatum, consisted of both an increase in 5-hydroxyindoleacetic acid (5-HIAA) levels and a decrease in dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Since the 5-HIAA/5-hydroxytryptamine (5-HT) ratio was increased, whereas the DOPAC/dopamine (DA) and HVA/DA ratios were decreased, it was argued that nimodipine activated the serotonergic and inhibited the dopaminergic systems. The first effect was enhanced by fasting and, likewise, by drug administration repeated for 5 days, while the second was not affected by fasting, but disappeared after 5 days' treatment. The data obtained appeared to substantiate the usefulness of nimodipine to treat some disorders of the central nervous system.