The relationship between dopamine D-2 receptor polymorphism at the Taq1 A locus and therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients

Previous studies have demonstrated that subjects with one or two Al alleles of dopamine D-2 receptor (DRD2) polymorphism at the Taq1 A locus have lowe r DRD2 density than those with no A1 allele. The present study aimed to exa mine whether the Taq1 A DRD2 genotypes are related to therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients, The subjects were 25 acutely exacerbated schizophrenic inpatients who had received no medication for at least 1 month before the study. The fixed dos e (18 mg/day) of nemonapride was administered to each patient for 3 weeks, The clinical status was prospectively monitored by the Brief Psychiatric Ra ting Scale (BPRS) before, and 3 weeks after, the treatment. The Taq1 A geno types (A1 and A2 alleles) were determined by the polymerase chain reaction method. Three patients were homozygous for the Al allele, 11 were heterozyg ous for the A1 and A2 alleles, and 11 were homozygous for the A2 allele. Th e patients with one or two A1 alleles (n = 14) showed significantly higher percentage improvement in total BPRS and positive symptoms than those with no A1 allele (n = 11) after 3-week treatment while the percentage improveme nt in other subgrouped symptoms (negative, anxiety-depression, excitement a nd cognitive symptoms) was similar between the two genotype groups. The pre sent results suggest that the Taq1 A DRD2 polymorphism is related to early therapeutic response to nemonapride in schizophrenic patients, possibly by modifying the efficiency of DRD2 antagonism of the drug in the central nerv ous system. Pharmacogenetics 10:335-341 (C) 2000 Lippincott Williams & Wilk ins.