Antagonism of the antihypertensive action of guanethidine sulfate by desipramine hydrochloride

In five studies, the antihypertensive effect of guanethidine sulfate was significantly reversed by two antidepressants, desipramine hydrochloride and protriptyline hydrochloride. This reversal was not immediate, requiring many hours before maximum antagonism was seen. After discontinuation of desipramine, an average of five days was required for the antihypertensive action of guanethidine to reappear. Three similar studies demonstrated that the antihypertensive action of bethanidine sulfate, a guanethidine-related drug, was reversed by desipramine also. The reversal of bethanidine was more rapid than with guanethidine, with almost maximum antagonism appearing within four hours, while the delay in the reappearance of bethanidine's antihypertensive action was similar to that seen with guanethidine. A blockade by the antidepressants of the uptake of the antihypertensives to their active site within the sympathetic neuron is suggested as a mechanism for the antagonism.