Prolactin response to nemonapride, a selective antagonist for D2 like dopamine receptors, in schizophrenic patients in relation to Taq1A polymorphism of DRD2 gene.
The dopamine D2 receptor (DRD2) gene has a Taq1A restriction fragment length polymorphism yielding two alleles, A1 and A2. It has been shown that the subjects with less frequent allele, the A1 allele, have lower density and diminished function of DRD2 in the striatum, compared to those with no A1 allele. In the present study, the relationship between this polymorphism and prolactin response to nemonapride, an antipsychotic drug with selective and potent DRD2 antagonistic property, was investigated in 25 Japanese schizophrenic inpatients (13 males, 12 females). The daily dose of nemonapride was fixed at 18 mg, and the duration of treatment was 3 weeks. Taq1A genotypes were determined by the polymerase chain reaction method. Plasma prolactin concentrations were measured by enzyme immunoassay. The subjects were divided into four subgroups by gender and Taq1A genotypes, i.e., six males and eight females with the A1 allele, seven males and four females with no A1 allele. The (delta)prolactin (change from the pretreatment concentration) at 1 week was significantly (P<0.05) higher in females with the A1 allele (78.0 +/- 47.1 ng/ml) than in males with the A1 allele (33.4 +/- 14.0 ng/ml) or with no A1 allele (29.5+/-24.8 ng/ml). In addition, (delta)prolactin at 3 weeks was significantly (P<0.05) higher in females with the A1 allele (98.1+/-67.9 ng/ml) than in females with no A1 allele (33.4+/-24.6 ng/ml), males with the A1 allele (29.1+/-17.3 ng/ml) or males with no A1 allele (28.6+/-22.0 ng/ml). The present study thus suggests that female patients with the A1 allele show a greater prolactin response to nemonapride, who may have a high risk for adverse effects associated with neuroleptic-induced hyperprolactinemia.