What Does 5-HT_2A Receptor Blockade Add to Clozapine's Effectiveness?

Clozapine's effectiveness in the treatment of schizophrenia has been attributed to its combination of 5-HT_2A receptor blockade and its relatively low D₂ receptor blocking affinities. However, few studies have examined in vivo 5-HT_2A receptor blockade in older conventional neuroleptics. This study used PET scans and [18F] setoperone, a radioligand with a high affinity for cortical 5-HT_2A receptors, to compare receptor binding of chlorpromazine (75 to 700 mg/day), clozapine (200 to 600 mg/day), and amisulpride (200 to 1200 mg/day) in patients with chronic schizophrenia.

Earlier in vitro studies have shown chlorpromazine to have high 5-HT_2A receptor binding affinity. Amisulpride is known to have high affinity for D₂ and D₃ receptors but not to …