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Published on: March 17, 2019
Antipsychotic efficacy: relationship to optimal D2-receptor occupancy
Luca Pani1, Luigi Pira, Giorgio Marchese
1PharmaNess S.c.a.r.l, Technological Park-Sardegna Ricerche, Pula (CA), Italy. luca.pani@pharmaness.it
Summary
Optimal dopamine D2-receptor occupancy (65-80%) is key for antipsychotic efficacy and tolerability. Further research is needed to refine D2-receptor blockade duration and brain region targets for improved schizophrenia treatment.
Area of Science:
- Neuroscience
- Psychopharmacology
- Radiology
Background:
- Antipsychotic agents and formulations vary significantly in safety and tolerability.
- Biochemical interactions between antipsychotics and dopamine D2-receptors influence these clinical differences.
Purpose of the Study:
- To review the relationship between antipsychotic receptor occupancy and clinical response.
- To explore the concept of a therapeutic window for D2-receptor occupancy.
Main Methods:
- Literature search using keywords: 'antipsychotic', 'neuroleptic', 'receptor', 'occupancy', 'dopamine', 'D2'.
- Inclusion of imaging and clinical data.
- Consideration of pharmacokinetic and pharmacodynamic properties.
Main Results:
- Imaging and clinical data support a therapeutic window for D2-receptor occupancy in the striatum (approx. 65-80%).
- Pharmacokinetic and pharmacodynamic properties are crucial for evaluating therapeutic effects.
Conclusions:
- Optimal D2-receptor occupancy is essential for balancing efficacy and tolerability in antipsychotic treatment.
- Further research, including preclinical studies, is required to determine optimal D2-receptor occupancy in different brain regions and blockade durations for atypical antipsychotics.
- Improving treatment outcomes for schizophrenia patients necessitates maximizing efficacy and tolerability profiles.
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