Some pharmacological actions of nisoxetine, a bicyclic inhibitor of noradrenaline uptake.

Some peripheral actions of the phenoxyphenylpropylamine, nisoxetine, have been compared with those of the tricyclic antidepressant, desipramine. The two drugs were equipotent in inhibiting the accumulation of 3H-noradrenaline by the sympathetic nerve terminals of the rat vas deferens; and, in low doses, equipotent in potentiating the actions of noradrenaline at both alpha 1- and alpha 2-adrenoceptors in this tissue. In the vas deferens, the alpha 1-adrenoceptor blocking action of desipramine was evident at concentrations of 0.1 mumol l-1 and above; nisoxetine was less potent. Neither drug exhibited antagonist actions at alpha 2-adrenoceptors. Nisoxetine was also less potent than desipramine in inhibiting responses to histamine, carbachol and bradykinin on the guinea-pig isolated ileum. Thus nisoxetine is the more specific of the two neuronal uptake inhibitors and may be a useful tool to block neuronal uptake in experiments designed to classify adrenoceptors in other tissues.