A new pharmacological approach to the diagnosis of hyperprolactinaemic states: the nomifensine test

Abstract

Abstract. The prolactin-(Prl) lowering effect of nomifensine (Nom), an antidepressant drug which activates dopamine (DA) neurotransmission mainly by inhibiting DA re-uptake in the central nervous system (CNS), was investigated in normoprolactinaemic subjects, in subjects with physiological puerperal hyperprolactinaemia or pathological hyperprolactinaemia. Nom (200 mg po) administered to 23 normoprolactinaemic women induced a significant decrease in baseline Prl, which was more marked (about 50% inhibition at 120 min) and prompt (30 min) in the subjects who had 'high' Prl levels (>12<20 ng/ml) (13 subjects) than in those with 'low' Prl levels (≤ 12 ng/ml). Also in 9 puerperal women (postpartum day 2) oral administration of 200 mg Nom was followed by a clear-cut decrease of base-line Prl, which started at 30 min and reached nadir values at 150–180 min (about 60% inhibition). Administration of Nom (200 mg po) to 47 subjects with pathological hyperprolactinaemia evidenced the presence of Nom non-responder (36 cases) or responder (11 cases) subjects. In 22 of the Nom non-responder subjects the existence of a Prl-se creting pituitary tumour was established at surgery by selective removal of an adenoma via the transsphenoidal route; of the 14 subjects who did not undergo surgery, 1 had evident and 5 had minor alterations of the sella turcica and, in addition, in 3 subjects the duration of amenorrhoea was longer than 5 years. Only 5 subjects of this group had no radiological alterations of the sella turcica, in presence of basal Prl levels ranging between 50–126 ng/ml. In contrast, 10 out of the 11 Nom-responder subjects had a radiologically normal sella turcica and basal Prl levels lower than 50 ng/ml. Administration of 2-Br-α-ergocriptine (2.5 mg po), a direct stimulant of pituitary DA receptors, to subjects with pathological hyperprolactinaemia (39 cases) induced a striking fall in plasma Prl levels (about 80% inhibition at 240 min), irrespective of the type of Prl responsiveness to Nom. These results indicate that Nom lowers plasma Prl levels in both normoprolactinaemic and hyperprolactinaemic subjects; in the latter, by virtue of its ability to affect selectively DA neurotransmission in the CNS, the drug appears capable of discriminating between individuals with and without pituitary adenoma.