Therapeutic implications of dopamine D4 vs. D2 receptor selectivity and occupancy

Abstract Clozapine and melperone exhibit higher affinity for the dopamine D 4 receptor than the D 2 receptor. Raclopride and chlorpromazine exhibit high selectivity for the dopamine D 2 receptor. D 4 selective compounds have a low incidence of EPS and TD, whereas D 2 selective compounds have a higher incidence. It is postulated that a drug's affinity for the D 4 receptor may confer antipsychotic activity and its affinity for the D 2 receptor may confer EPS and/or TD activity.