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Prolactin-Lowering and- Releasing Drugs

Mechanisms of Action and Therapeutic Applications

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Summary

Drugs whose systemic and/or central administration induce suppression or stimulation of prolactin secretion are reviewed. The most commonly used prolactin-lowering drugs include: (a) direct acting dopamine receptor agonists (e.g. dopamine, apomorphine and the ergot derivatives); (b) indirect-acting dopamine agonists (e.g. amphetamine, nomifensine, methylphenidate, amineptine); (c) drugs which impair serotoninergic neurotransmission (e.g. the neurotoxin 5,7-dihydroxytryptamine and the serotonin receptor antagonists methysergide and metergoline); (d) γ-aminobutyric acid [GABA]-mimetic drugs (e.g. GABA, muscimol, ethanolamine-O-sulphate, sodium valproate); (e) histamine H2-receptor agonists; and (f) cholinergic (muscarinic and nicotinic) receptor agonists. Major prolactin-stimulating agents comprise: (a) dopamine receptor antagonists (e.g. classic and atypical antipsychotic drugs); (b) drugs differently capable of impairing central nervous system dopamine function (e.g. blockers of dopamine neurotransmission such as α -methyl-p-tyrosine and 3-iodo-L-tyrosine, false precursors such as α-methyldopa, and inhibitors of L-aromatic amino acid decarboxylase such as carbidopa and benserazide); (c) drugs enhancing serotoninergic neurotransmission (e.g. the serotoninergic precursors tryptophan and 5-hydroxytryptophan, direct-acting serotonin agonists such as quipazine and MK 212, and indirect-acting serotonin agonists such as fenfluramine); (d) blockers of serotonin reuptake (e.g. fluoxetine, fluvoxamine and clovoxamine); (e) H1-receptor agonists; and (f) H2-receptor antagonists (e.g. cimetidine).

Some of the above classes of drugs (e.g. the indirect-acting dopamine agonists, dopamine receptor antagonists, GABA-mimetic drugs, dopamine receptor blocking drugs, and H2-antagonists) may be useful for selecting among hyperprolactinaemic patients those with a prolactin-secreting tumour in an early stage of the disease. Direct-acting dopamine receptor agonists, notably the ergot derivatives; are potent antigalactopoietic agents, can revert impaired gonadal function to normal in both female and male patients with hyperprolactinaemia, and may have antiproliferative effects on pituitary prolactin-secreting tumours. All prolactin-stimulating agents, but especially the dopamine receptor antagonists, are liable to induce alterations in gonadal function in subjects of either sex.

In addition to their usage for diagnostic or therapeutic purposes, the above drugs appear to be invaluable tools for enabling a better understanding of the neurotransmitter control of prolactin secretion.

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  1. Department of Pharmacology, University of Milan, Via Vanvitelli, 32-20129, Milan, Italy

    Eugenio E. Müller, V. Locatelli, S. Cella, A. Peñalva, A. Novelli & D. Cocchi

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Müller, E.E., Locatelli, V., Cella, S. et al. Prolactin-Lowering and- Releasing Drugs. Drugs 25, 399–432 (1983). https://doi.org/10.2165/00003495-198325040-00004

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