title: DRD2 Taq1A polymorphism modulates prolactin secretion induced by atypical antipsychotics in healthy volunteers.
abstract: Hyperprolactinemia mediated by antagonism of dopaminergic neurotransmission in the pituitary gland is a common adverse effect of antipsychotics. Recent studies have suggested that polymorphisms of dopamine receptors can affect the therapeutic response to antipsychotics. Thus, our aim was to evaluate whether 2 such polymorphisms (DRD2 Taq1A and DRD3 Ser9Gly) modulate prolactin release in healthy volunteers (n = 119) receiving a single dose of quetiapine (25 mg, n = 26), olanzapine (5 mg, n = 57), or risperidone (1 mg, n = 36). The increases in maximum concentration and in area under the curve were calculated from plasma prolactin levels after subtraction of pretreatment levels. Multiple regression analyses revealed that prolactin increases in maximum concentration and in area under the curve depended on drug (quetiapine < olanzapine < risperidone; P < 0.001), sex (women > men; P < 0.001), and Taq1A polymorphism (A1⁺ > A2/A2; P < 0.05). Analysis of the individual drugs revealed that prolactin secretion was modulated by sex and Taq1A polymorphism in olanzapine and risperidone (P < 0.05); however, these factors were not linked to prolactin secretion in quetiapine.
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: López-Rodríguez
authors.forename: Manuel
authors.initials: M
authors.lastname: Román
authors.forename: Jesús
authors.initials: J
authors.lastname: Novalbos
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Pelegrina
authors.forename: Dolores
authors.initials: D
authors.lastname: Ochoa
authors.forename: Francisco
authors.initials: F
authors.lastname: Abad-Santos
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001569:Benzodiazepines / Q000494:pharmacology; D003987:Dibenzothiazepines / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011110:Polymorphism, Genetic; D011388:Prolactin / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D000069348:Quetiapine Fumarate; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D012044:Regression Analysis; D018967:Risperidone / Q000494:pharmacology; D012737:Sex Factors
chemical_list: D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D003987:Dibenzothiazepines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D011388:Prolactin; D018967:Risperidone; D000077152:Olanzapine