Comparative cardio-inhibitory effects of certain cyclohexanol and cyclohexylamine derivatives

Abstract

Derivatives of cyclohexanol and cyclohexylamine were pharmacologically screened for cardioplegic effects on intact anesthetized rats, and isolated guinea pig hearts. Evaluation of potency was based on the ability to depress rat carotid blood pressure, and to produce cardiac arrest in the isolated guinea pig heart.As a group, the non-ethynyl cyclohexanol derivatives were more potent in producing a hypotensive response, than were the derivatives of cyclohexylamine. trans-2-£-Tolyl-cis-l, 4-cyclohexanediol and trans-2-£-tolyl-trans-l, 5-cyclohexanediol were equally effective and the most active. trans-2-(E.-Chlorophenyl)-N, N-dimethylcyclohexyl~ amine was the least active, and the only compound to produce a pressor response.Conversely, the cyclohexylamines were more potent cardioplegic agents. The cis and trans isomers of 2-(E.-chlorophenyl)-N, N-dimethyl cyclohexylamine were equally the most active with trans-2-£-tolylcis-l, 4-cyclohexanediol the least active. The minimum effective cardioplegic dose of l-ethynyl-trans-2-£-tolylcyclohexanol was also the cardiotoxic dose as the heart failed to recover from arrest.Mechanism studies on spontaneously beating isolated rat atria indicate an antagonistic effect between calcium and the negative inotropic action of these compounds.