DANTROLENE AND AZUMOLENE INHIBIT [H-3] PN200-110 BINDING TO PORCINE SKELETAL-MUSCLE DIHYDROPYRIDINE RECEPTORS

We tested whether the hydantoin muscle relaxants dantrolene, azumolene, or aminodantrolene could alter the binding of [3H]PN200-110 to transverse tubule dihydropyridine receptors or the binding of [3H]ryanodine to junctional sarcoplasmic reticulum Ca2+ release channels. All three drugs inhibited [3H]PN200-110 binding with azumolene (IC50≈20 μM) 3-5 times more potent than dantrolene or aminodantrolene. In contrast, 100 μM azumolene and dantrolene produced a small inhibition of [3H]ryanodine binding (<25%) while amino- dantrolene was essentially inert. Hence there was a preferential interaction of hydantoins with dihydropyrdine receptors instead of ryanodine receptors. Skeletal muscle dihydropyridine receptors may participate in the mechanism of action of dantrolene and azumolene. © 1992.