Analysis of neuroleptic binding affinities and potencies for the different human D2 dopamine receptor missense variants.
Neuroleptics, or antipsychotics, are widely used for the treatment of psychotic symptoms such as hallucinations and delusions in schizophrenia and other psychiatric disorders. Pharmacotherapy of these diseases is frequently complicated by a great variability in the clinical response to neuroleptics and by the development of serious and potentially life-threatening side-effects. Brain D2 dopamine receptors are one of the major targets of neuroleptic treatment. The human D2 dopamine receptor (DRD2) gene has three variants predicting the amino acid substitutions Ser311Cys, Pro310Ser and Val96Ala in the receptor protein. We show that several typical and atypical neuroleptics commonly used in the treatment of psychotic disorders have differences in binding affinities and potencies for the D2 dopamine receptor variants. Functional differences between dopamine receptor variants might be related to genetically determined differences in response to neuroleptic treatment.
Cravchik
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A
Unit on Molecular Clinical Investigation, Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland, USA. cravchik@helix.nih.gov
Sibley
D R
DR
Gejman
P V
PV
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D065127:Dopamine D2 Receptor Antagonists; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D020125:Mutation, Missense; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D005576:Colforsin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins