[Interaction of phenothiazinic anti-inflammatory agent, protizinic acid, with the biopolymers: Inhibitory effects on functions of platelets (author's transl)].

: Two types of phenothiazinic anti-inflammatory agents, protizinic acid (PZA) and metiazinic acid (MZA) were examined using 1) heat denaturation test, 2) heat-induced erythrocyte lysis, 3) several platelet functions, 4) model membrane systems containing the same phospholipids and cholesterol compositions as in platelets. PZA and MZA were inhibited with heat denaturation in a similar manner seen with BSA and heat-induced erythrocyte lysis, and effects were more potent than indomethacin (IM). PZA showed inhibitory effects similar to MZA on ADP or collagen-induced platelet aggregation. However, in arachidonic acid (AA)-induced rabbit platelet aggregation, PZA had a more potent effect, similar to effects seen with IM and more potent than those of MZA. PZA inhibited the lethal effect of AA in rabbits at concentrations lower then MZA. To determine the sites of action, we examined the effects on uptake and release reactions of 3H-serotonin. PZA and MZA did not affect the uptake reaction but did reduce the release of serotonin to a greater extent than seen with IM. The tested drugs had little effect on the platelet aggregation in vivo. To investigate the interaction of these drugs with lipid bilayers, we used liposomes as a model membrane, of which the lipids compositions were the same as that of platelets. The tested drugs showed inhibitions of the liposome aggregation with addition of 6 mM Ca2+, in a dose dependent manner and similar to findings in the drug-platelet system. In this experiment, PZA had a more potent interaction with lipid bilayers than did MZA. These results suggest that interactions of PZA with the platelet membrane may be the origin of the PZA-induced inhibition of the platelet aggregation, in addition to the effect on the biosynthesis of prostaglandins.