Analysis of neuroleptic binding affinities and potencies for the differenthuman D-2 dopamine receptor missense variants

Neuroleptics, or antipsychotics, are widely used for the treatment of psych otic symptoms such as hallucinations and delusions in schizophrenia and oth er psychiatric disorders. Pharmacotherapy of these diseases is frequently c omplicated by a great variability in the clinical response to neuroleptics and by the development of serious and potentially life-threatening side-eff ects. Brain D-2 dopamine receptors are one of the major targets of neurolep tic treatment. The human D-2 dopamine receptor (DRD2) gene has three varian ts predicting the amino acid substitutions Ser311Cys, Pro310Ser and Val96Al a in the receptor protein. We show that several typical and atypical neurol eptics commonly used in the treatment of psychotic disorders have differenc es in binding affinities and potencies for the D-2 dopamine receptor varian ts. Functional differences between dopamine receptor variants might be rela ted to genetically determined differences in response to neuroleptic treatm ent. Pharmacogenetics 9:17-23 (C) 1999 Lippincott Williams & Wilkins.