Cardiovascular peripheric effects of a new tricyclic antidepressant, cianopramine (Ro 11-2465) in dogs

In acute experiments in dogs anesthetized with pentobarbital, pressor responses produced by the i.v. injection of serotonin, noradrenaline and electric stimulation of the sympathetic nerves of the spleen, were registered before the i.v. injection of cianopramine (Ro 11-2465), a potent inhibitor of the uptake of serotonin into 5-HT neurones. Doses of 0.1 to 0.5 mg/kg of the antidepressant did not modify the blood pressure, while these produced a more intensive and prolonged pressor response during the i.v. injection of serotonin (p less than 0.05), noradrenaline (p less than 0.001) and stimulation of the splenic nerves (p less than 0.005). These effects resulted from the inhibition of the presynaptic reuptake of monoamines. The i.v. injection of 1-2 mg/kg of cianopramine produced significant hypotension (p less than 0.001) with baroreceptor and serotoninergic responses blockade. An induced strong hypertensive dose-dependent effect was observed after the i.v. administration of noradrenaline (+82%) and stimulation of splenic nerves (+80%). Cianopramine did not affect the hypotension produced by carbachol and histamine. The peripheric action of cianopramine showed a higher inhibitory effect on the presynaptic reuptake of noradrenaline than on serotonin.