Endocrine Profile and Therapeutic Employment of a New Prolactin-Lowering Drug, Metergoline

Abstract

Metergoline is an ergoline derivative with potent peripheral and central antiserotoninergic properties which has recently been shown to possess a marked prolactin (PRL)-lowering activity. This drug significantly decreases serum PRL levels after acute administration in normal subjects, in puerperal women, and in most hyperprolactinemic patients with or without pituitary tumor. Its PRL-lowering effect is unaffected by pimozide pretreatment in healthy subjects, and is frequently dissociated from that of bromocriptine in hyperprolactinemic patients. The drug does not affect the secretion of growth hormone (GH), thyrotropin and gonadotropins, while it blunts the corticotropin response to centrally but not peripherally-acting stimuli in normal subjects. In acromegalics, metergoline reduces serum PRL as well as GH levels, both actions being prevented by pimozide pretreatment. Improvement in oral glucose tolerance with unchanged insulin secretion is observed after a short course of metergoline treatment in patients with chemical diabetes. The PRL-lowering action of the drug is sustained during chronic treatment in hyperprolactinemic subjects. Inhibition of puerperal lactation may be obtained by a few days metergoline treatment in almost all treated women. Normalization of serum PRL levels and restoration of cyclic ovarian function are achieved within 1–4 months of treatment with the drug in most women with hyperprolactinemic amenorrhea. The possible role of metergoline in the treatment of other endocrine disorders such as normoprolactinemic amenorrhea, sexual impotence, Cushing’s disease, acromegaly and mild diabetes mellitus remains to be determined. Although the PRL-lowering effect and the therapeutic employment of metergoline

Inhibition of Puerperal Lactation by Metergoline: Interactions with Methylergobasine Maleate

“…In the present study we found that metergoline, at the dose of 8 or 12 mg/day for 5 days, is able to inhibit puerperal lactation in most of puerperae, thus confirming previous studies concerning the effectiveness of metergoline in the prevention of puerperal lactation [7][8][9]. Whereas no sig nificant clinical difference was found between the two dosages, the effect of metergoline on PRL release appeared to be dose-related, the higher dosage exerting a quicker and more evident effect than the lower dosage.…”

“…On the other hand, serotonin stimulates PRL release [5], while antiserotoninergic drugs like metergoline, methysergide and cyproheptadine inhibit PRL release [6]. In particular, metergoline is now widely employed in the prevention of puerperal lacta tion [7][8][9]. During the puerperium, uterine contractions are routinely pro moted by the administration of methylergobasine maleate (MEM).…”

Influence of the serotonin antagonist, metergoline, on the anxiogenic effects of carbon dioxide, and on heart rate and neuroendocrine measures, in healthy volunteers

“…Cortisol was unaffected by metergoline, whereas prolactin was lowered by it, as expected for a 5-HT antagonist (Ferrari et al, 1980;Goodall et al, 1993;Jorgensen et al, 1992;Quattrone et al, 1983). Metergoline also possesses some dopamine agonist properties (Ellis et al, 1991), which could also explain lowered prolactin levels, but it binds dopamine less ef®ciently than 5-HT by one to two orders of magnitude (Hamon et al, 1981).…”

Further studies of the putative serotonin agonist, m-chlorophenylpiperazine: Evidence for a serotonin receptor mediated mechanism of action in humans

“…However, additional evidence regarding the serotonergic basis of m-CPP's effects in humans is needed before the drug can be considered a useful probe of 5HT receptor responsivity in man (Checkley ~980). To further examine the role of 5HT in m-CPP-induced hormonal and temperature changes in humans, we studied the effects of acute oral administration of m-CPP in a group of healthy adults before and after pretreatment with the 5HT antagonist metergoline (Ferrari et al 1980).…”