Antipsychotic efficacy: relationship to optimal D2-receptor occupancy.
Clinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords 'antipsychotic or neuroleptic', 'receptor' and 'occupancy' and 'dopamine' and 'D2' supplemented by the authors' knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a 'therapeutic window' between approximately 65 and approximately 80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia.
Pani
Luca
L
PharmaNess S.c.a.r.l, Technological Park-Sardegna Ricerche, Pula (CA), Italy. luca.pani@pharmaness.it
Pira
Luigi
L
Marchese
Giorgio
G
D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D003692:Delayed-Action Preparations; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D017448:Receptors, Dopamine D2; D004298:Dopamine