Selective inhibition by dantrolene of caffeine-induced catecholamine release from perfused dog adrenals

Effects of dantrolene sodium on catecholamine (CA) release from the perfused dog adrenal medulla was investigated in relation to it's therapeutic action on malignant hyperthermia (MH), in which CAs would play a significant pathophysiological role. Acetylcholine (ACh)-induced CA release was not affected, whereas caffeine-induced CA release was inhibited by dantrolene in a dose-dependent manner (84% inhibition at 10 microM). Dantrolene had no effect on the CA release induced by lasalocid or Na+ deprivation. On the other hand halothane inhibited ACh-induced CA release markedly, Na+ deprivation-induced CA release slightly, but not caffeine-induced CA release at all. The results indicate that dantrolene selectively inhibit caffeine-induced CA release, and that the therapeutic action of dantrolene on MH would be, at least in part, due to inhibition of abnormal release of Ca2+ in the adrenal medullary cells.