title: Drug-induced hypo- and hyperprolactinemia: mechanisms, clinical and therapeutic consequences.
abstract: BACKGROUND
  The altered profiles of prolactin secretion in the anterior hypophysis, generated by pathological, pharmacological or toxicological causes, have special consequences on multiple functions in both genders.
  
  
  METHODS
  This selective review presents the main mechanisms controlling prolactin secretion, focusing on the interplay of various neurotransmitters or xenobiotics, but also on the role of psychic or posttraumatic stress. A detailed analysis of several pharmacotherapeutic groups with hyperprolactinemic effects emphasize on the relevance of the pharmacokinetic/pharmacodynamic mechanisms and the clinical significance of the long term administration.
  
  
  CONCLUSIONS
  Accurate monitoring and evaluation of the hyperprolactinemia induced by xenobiotics is strongly recommended. The typical antipsychotics and some of the atypical agents (amisulpride, risperidone, paliperidone), as well as some antidepressants, antihypertensives and prokinetics, are the most important groups inducing hyperprolactinemia. The hyperprolactinemic effects are correlated with their affinity for dopamine D2 receptors, their blood-brain barrier penetration and, implicitly, the requested dose for adequate occupancy of cerebral D2 receptors. Consequently, integration of available pharmacokinetic and pharmacodynamic data supports the idea of therapeutic switch to non-hyperprolactinemic agents (especially aripiprazole) or their association, for an optimal management of antipsychotic-induced hyperprolactinemia. Possible alternative strategies for counteracting the xenobiotics-induced hyperprolactinemia are also mentioned.
authors.affiliation: University of Medicine and Pharmacy Carol Davila, Faculty of Medicine, Department of Clinical Pharmacology, Toxicology and Psychopharmacology, Bucharest 011643, Romania. victor.voicu@yahoo.com
authors.forename: Victor
authors.initials: V
authors.lastname: Voicu
authors.forename: Andrei
authors.initials: A
authors.lastname: Medvedovici
authors.forename: Aurelian Emil
authors.initials: AE
authors.lastname: Ranetti
authors.forename: Flavian Ştefan
authors.initials: FŞ
authors.lastname: Rădulescu
mesh_terms: D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D000068180:Aripiprazole; D001812:Blood-Brain Barrier / Q000378:metabolism; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced* / Q000473:pathology; D007555:Isoxazoles / Q000009:adverse effects / Q000493:pharmacokinetics; D000068882:Paliperidone Palmitate; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics; D015363:Quinolones / Q000009:adverse effects / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D018967:Risperidone / Q000009:adverse effects / Q000493:pharmacokinetics; D013315:Stress, Psychological; D013469:Sulpiride / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D015262:Xenobiotics / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D010879:Piperazines; D011743:Pyrimidines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D015262:Xenobiotics; D013469:Sulpiride; D000077582:Amisulpride; D000068180:Aripiprazole; D011388:Prolactin; D018967:Risperidone; D000068882:Paliperidone Palmitate