Selective effects of diltiazem, a benzothiazepine calcium channel blocker, and diazepam, and other benzodiazepines on the Na+/Ca2+ exchange carrier system of heart and brain mitochondria.

Diltiazem, diazepam, and clonazepam effectively inhibit Na+-induced Ca2+ release from mitochondria isolated from rabbit heart and rat brain. At 10 mM NaCl, the 50% inhibition of the rate of Ca2+ release occurred at 5, 7, 40 and 350 microM of clonazepam d-cis-diltiazem, diazepam and 1-cis-diltiazem, respectively. Ro 15-1788 (imidazobenzodiazepine), a pharmacological antagonist presumably at the high affinity site of diazepam, had no effect either alone or in combination with diltiazem or diazepam. We suggest that the Na+/Ca2+ exchange carrier in mitochondria may be a common receptor for diltiazem and diazepam.