Selective inhibition of prostaglandin biosynthesis by antipsychotic drugs

The effects of antipsychotic drugs on arachidonic acid metabolism via prostaglandin [PG] endoperoxide synthase and lipoxygenase pathways were determined. Chlorpromazine, thioridazine, fluphenazine, haloperidol, promethazine and cyclizine, in decreasing order of potency, inhibited PG endoperoxide synthase [thus PG biosynthesis] in a dose related manner. Conversely, anti-psychotic drugs either stimulated or had no effect on lipoxygenase activity. These results demonstrate that antipsychotic drugs selectively inhibit PG biosynthesis. Since administration of PGs in man produces emesis, and other untoward effects; our data is suggestive that the anti-emetic action of anti-psychotic drugs could be due to their inhibition of PG biosynthesis