The importance of serotonin-dopamine interactions in the action of clozapine

Clozapine has an affinity for the dopamine (DA) D₂ receptor which is relatively weak but is in line with its average clinical dose when compared with typical neuroleptic drugs. A few atypical antipsychotic drugs may have high absolute affinities for the D₂ receptor, but most are weak D₂ blockers. The atypical antipsychotic drugs also differ from the typical antipsychotic drugs by a relatively high affinity for the serotonin (5-HT₂) receptor. This is evident on both in vitro and in vivo binding to cortical 5-HT₂ receptors. The atypical antipsychotics are best distinguished from the typical antipsychotics on the basis of the relationship between strong 5-HT₂ and weak D₂ affinities. High D₁ receptor binding is not characteristic of the group of atypical drugs. A new group of putative atypical antipsychotic drugs with high affinities for 5-HT₂ compared to D₂ receptors is under study.