Effect of diclofensine, a novel antidepressant, on peripheral adrenergic function

Diclofensine is a novel antidepressant with equipotent inhibitive effects on the neuronal uptake of norepinephrine (NE), serotonin, and dopamine. It is devoid of monoamine-releasing or monoaminoxidase-inhibiting properties. The action of diclofensine on peripheral neuronal adrenergic function was studied through tests of the blood pressure response to NE, tyramine, and phenylephrine (PE). The blood pressure response to NE was enhanced and that to tyramine was decreased by diclofensine, as a result of its inhibitive action on peripheral neuronal amine uptake. PE sensitivity was also enhanced by diclofensine as well as after a single dose of desmethylimipramine (DMI). In contrast to the common opinion that PE does not interact with the neuronal uptake mechanism, the increase in PE-induced blood pressure response after diclofensine and DMI suggests that PE, a nonbiogenic amine, does indeed enter into the peripheral adrenergic neuron. This neuronal uptake may probably be unmasked only by powerful NE uptake inhibitors such as DMI or diclofensine.