Current Opinione on the Role of Dopamine D(2) and D(3) Receptors in theMechanism of Action of Neuroleptics in the Treatment of Schizophrenia

Overview

Mechanism of Action of Neuroleptics in the Treatment of SchizophreniaAlthough atypical antipsychotics are becoming the treatment of choice for schizophrenia, whatmakes the antipsychotic „atypical“, is not clear [3]. New Findings based on research using positronemission tomography (PET) were published recently. Schizophrenic patients have increasedsynaptic dopamine concentrations in the striatum; antipsychotics with high affi nity for dopamineD(2) receptors are associated with a substantial increase in D(2) receptor binding; Columbia studyprovides an important indication of hyperdopaminergic function in schizophrenia; antipsychoticeffi cacy of atypical antipsychotics has been observed at lower D(2) receptor occupancy rates thanwith typical neuroleptics. Based on this and other new fi ndings the Schizophrenia research groupin Toronto propose than fast dissociation from the D(2) receptor makes an antipsychotic moreaccomodating of physiological dopamine transmision, permitting an antipsychotic effect withoutmotor side effects. In contrast to the multireceptor hypotheses, the authors predict that the atypicalantipsychotic effect can be produced by appropriate modulation of the D(2) receptor alone; theblockade of other receptors is neither necessary nor suffi cient.

Key words:
schizophrenia, dopamine hypothesis, D(2) receptors, fast dissociation from the D(2)receptor.