Investigation into the inotropic mechanisms of sulmazole.

A calcium ionophorous action of sulmazole (AR-L 115 BS, Vardax) as a cause of its positive inotropic action could be excluded because the drug did not carry calcium ions across a lipid barrier. Sulmazole at concentrations of 1-10 mmol/l induced contractures in the isolated rat diaphragma as effectively as caffeine. Both drugs also gave rise to contracture in the absence of extracellular calcium ions indicating the liberation of calcium from intracellular sites. Sulmazole precipitated contracture anew in partially relaxed atria of the guinea pig after long-standing (1 h) withdrawal of extracellular sodium. This effect of sulmazole was concentration-dependent (0.1-1 mmol/l), as was that of caffeine (1-10 mmol/l) in this preparation. As the concentration-response curves of the drugs were parallel and were shifted by procaine in a parallel manner to the right, this action of sulmazole can be described as "caffeine-like". Sulmazole (0.033-1 mmol/l) displayed its positive inotropic action particularly at the lower rates of atrial contraction and inhibited the effect of poststimulatory potentiation. In the range of higher concentrations and rates of contraction, increases in diastolic tension occurred. In atria with a steady-state contractility being almost completely suppressed by nifedipine (3.3 mumol/l), sulmazole (0.33-1 mmol/l) restored contractile force while caffeine (2-8 mmol/l) did not. These results show that the positive inotropic action is neither due to a "caffeine-like" effect nor related to the slow inward current.(ABSTRACT TRUNCATED AT 250 WORDS)