Table 2.

Hypotheses for clozapine’s superior therapeutic efficacy based on neuroreceptor binding profiles

Hypothesis	Evidence for hypothesis (aspects of clozapine)	Evidence against hypothesis (aspects of less efficacious antipsychotics)
Dopamine D2 receptor	Low D2 receptor occupancy Rapid D2 receptor dissociation	Quetiapine: low D2 receptor occupancy Quetiapine: rapid D2 receptor dissociation
Dopamine D4 receptor	High D4 receptor affinity High D4/D2 receptor affinity ratio	Olanzapine: high D4 receptor affinity Ziprasidone: high D4 receptor affinity Asenapine: high D4/D2 receptor affinity ratio D4 receptor antagonists ineffective
Serotonin receptors	High 5-HT2A/D2 receptor affinity ratio	Most atypical antipsychotics: high 5-HT2A/D2 receptor affinity ratio Amisulpride: low 5-HT2A receptor affinity (but highest efficacy after clozapine) 5-HT2A receptor antagonists ineffective

5-HT = 5-hydroxytryptamine