Flumezapine and zotepine: 5-hydroxytryptamine antagonism not involved in the lack of synergism of these antipsychotic drugs with amfonelic acid in rats.

Two antipsychotic drugs, flumezapine and zotepine, resembled clozapine, not spiperone, in not acting synergistically with amfonelic acid to elevate striatal concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in rats. Since flumezapine, zotepine and clozapine antagonize 5-hydroxytryptamine (5-HT) receptors with potency similar to their potency in antagonizing dopamine receptors, the possibility that 5-HT receptor blockade prevented their synergism with amfonelic acid was considered. Methiothepin, a potent 5-HT antagonist and dopamine antagonist, mimicked spiperone in causing a marked increase in striatal DOPAC in amfonelic acid-treated rats, indicating that 5-HT antagonism is not involved in the lack of synergism of flumezapine and zotepine with amfonelic acid.