Abstract

Dimethyl sulfoxide (DMSO) and other dipolar aprotic solvents [dimethylformamide (DMF), dimethylacetamide, acetonitrile and sulfolane] were found to possess positive inotropic activity in the guinea-pig left atria. Hexainethylphoephoramide is one of the most strongly dipolar aprotic solvents known, and it elicited a dose-related negative inotropic response, as did the protic solvent polyethylene glycol-300. The dose-response curves of DMSO, DMF and dimethylacetamide were not affected by reserpine pretreatment of animals or by alpha-and beta-adrenergic receptor blocking agents, indicating that the positive inotropic response is not mediated through the release of catecholamines or through a direct "catecholamine-like" activity on adrenergic receptors. No evidence of tachyphylaxis was observed. DMSO also elicited a positive inotropic response in rabbit left atria, but a dose-related negative inotropic response in cat atria and papillary muscles, rat atria, dog trabeculae carneae and frog heart. DMF, on the other hand, caused a positive inotropic responsein all of these tissues except for frog heart, where responseswere variable. Dimethyl sulfone, the major metabolic product of DMSO also elicited a positive inotropic response. The activities of DMSO and DMF are discussed in relation to their physical constants and their activity on adenylcyclase, Na⁺, K⁺-dependent adenosine triphosphatase and microsomal Ca⁺⁺-transport adenosine triphosphatase.