Abstract
The antidepressant drugs, protriptyline, imipramine, amitriptyline and their desmethyl derivatives, have been demonstrated to be capable of inhibiting catecholamine depletion in hearts of mice induced by α-methyl-meta-tyrosine, metaraminol, guanethidine and 6-hydroxydopamine. These antidepressants also antagonized the action of guanethidine in reduring responses of the cat nictitating membrane and cardioacceleration in the dog elicited by sympathetic nerve stimulation. Related agents demonstrated to possess all or part of these antagonistic actions include cocaine, tripelennamine, pipradrol, methyiphenidate, chlorpromazine, promazine and desmethylpromazine.
The catecholamine-depleting effect of 6-hydroxydopamine was more readily blocked by these agents, as reflected by smaller doses required to demonstrate antagonism. α-Methyl-meta-tyrosine was next most readily influenced while metaraminol and guanethidine were the most resistant. Reserpine-induced depletion of heart was not reduced even by relatively large doses. In terms of potency, protriptyline proved to be the most active antagonist of the several agents studied, both in terms of preventing catecholamine depletion and antagonizing the neuron blocking action of guanethidine.
The findings are discussed in relation to other classes of agents found to have similar antagonistic actions versus catecholamine-depleting agents.
Footnotes
- Received October 7, 1963.
- Accepted January 3, 1964.
- The Williams & Wilkins Company
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