Diazepam-stimulated increases in the synaptosomal uptake of ⁴⁵ca²⁺: Reversal by dihydropyridine calcium channel antagonists

Pharmacologically relevant concentrations of benzodiazepines have previously been reported to increase ⁴⁵Ca²⁺ uptake into synaptosomes. This observation, coupled with the recent report that nifedipine may block the hypnotic effect of flurazepam, led us to study the effects of nifedipine and nitrendipine on ⁴⁵Ca²⁺ uptake into synaptosomes. Diazepam (1 μM) significantly increased the uptake of ⁴⁵Ca²⁺ to a crude synaptosomal fraction (P₂) prepared from rat cerebral corted and depolarized with 55 mM K⁺. Nifedipine (1 μM) did not alter the uptake of Ca²⁺, while nitrendipine (1 μM) reduced uptake by 37%. Both nifedipine and nitrendipine completely antagonized the ability of diazepam to increase ⁴⁵Ca²⁺ uptake following K⁺ depolarization. These observations support the notion that the pharmacologic actions of benzodiazepines may be mediated through effects on a calcium channel.