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

Dimethyl sulphoxide inhibits platelet aggregation and alters arachidonic acid metabolism

Dimethylsulphoxide [DMSO] inhibits human platelet aggregation induced by adrenaline, ADP, arachidonic acid [AA] or collagen in a concentration-related manner. DMSO produced strongest inhibitory effects against ADP-induced aggregation whereas it was a weak inhibitor of AA-induced aggregation. DMSO did not protect rabbits against death from pulmonary platelet thrombosis induced by AA. On the other hand, DMSO exerted differential effects against AA metabolism. It stimulated PG endoperoxide synthase while DMSO inhibited lipoxygenase activity. Since lipoxygenase products play an important role in inflammation, it is possible that inhibition of lipoxygenase by DMSO could lead to beneficial anti-inflammatory activity by comparison with classical PG endoperoxide synthase inhibitors such as aspirin-like drugs