Inactivation of hemolytic actiyities of serum complement by phenothiazines

Abstract

The hemolytic titers of human and guinea pig sera were greatly reduced by pretreatment with any of several phenothiazines. The anti-complement activity of the phenothiazines depended on the nature of substituents at positions 2 and 10. In the promazine group, the relative effectiveness of the position-2 substituents was in the order H > Cl > OCH3 > CF3. The presence of a piperazinyl group in the chain at position 10 conferred strong anti-complement activity. Thioridazine was the most potent inhibitor among the 12 phenothiazines studied. Complement components C′2 and C′4 in both human and guinea pig sera were more sensitive than other components to inactivation by phenothiazines. Phenothiazines administered orally in moderate doses did not lower the complement level of serum in three subjects. There was no correlation between anti-complement activity of the phenothiazines and their relative therapeutic potency.