Comparative cardio-inhibitory effects of certain cyclohexanol and cyclohexylamine derivatives

Derivatives of cyclohexanol and cyclohexylamine were screened for cardioplegic effects on intact anesthetized rats and isolated guinea pig hearts. Evaluation of potency was based on the ability of the compounds to depress rat carotid blood pressure, and to produce reversible arrest of the isolated guinea pig heart. trans-2-o-Tolyl-cis-1, 4-cyclohexanediol and trans-2-o-tolyl-trans-1, 5-cyclohexanediol were equally effective and the most active compounds tested in producing a hypotensive response. trans-2(p-Chlorophenyl)-N, N-dimethylcyclohexylamine was the least active and the only compound causing a pressor response. As a group, the cyclohexanol derivatives were more potent hypotensive agents than were the derivatives of cyclohexylamine. Conversely, the cyclohexylamines were more potent cardioplegic agents. The cis and trans isomers of 2-(p-chlorophenyl)-N, N-dimethylcyclo-hexylamine were equally the most active, with trans-2-o-tolyl-cis-l,4-cyclohexanediol the least active of the compounds studied. The minimum effective cardioplegic dose of 1-ethynyl-trans-2-o-tolylcyclohexanol was also the cardiotoxic dose as the heart failed to recover from arrest. Mechanism studies indicate an antagonistic effect between calcium and the negative inotropic action of these compounds.