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.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D005442:Flumazenil; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D012964:Sodium / Q000494:pharmacology*; D019831:Sodium-Calcium Exchanger
D001552:Benzazepines; D001570:Benzodiazepinones; D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D001569:Benzodiazepines; D005442:Flumazenil; D002998:Clonazepam; D012964:Sodium; D004110:Diltiazem; D003975:Diazepam; D002118:Calcium