Mechanism of the sympathomimetic action of cyclohexylamine and hexylamine: release of catecholamines from nerve endings.

The sympathomimetic effects of cyclohexylamine, a six-carbon cyclic aliphatic amine, and hexylamine, a six-carbon straight-chain aliphatic amine, were studied in open-chest dogs with an intact circulation, in dogs on cardiopulmonary bypass and in the isolated, perfused canine hindlimb. Both drugs produced dose-dependent augmentation of left ventricular dp/dt , right ventricular contractile force, heart rate and systemic arterial pressure. Depletion of endogenous catecholamine stores by reserpine or blockade of the neural uptake mechanism by cocaine abolished or significantly lessened these positive responses to both cyclohexylamine and hexylamine. It is concluded, therefore, that these two simple amines exert their sympathomimetic effects on the cardiovascular system indirectly, by causing the release of neuronally stored catecholamines. The observation that cyclohexylamine has such cardiovascular effects is of particular interest since it is the principal excreted metabolite of cyclamate, a chemical widely employed as a non-nutritive sweetening agent. However, cyclamate administered i.v. does not appear to affect the cardiovascular system.