Electronic Properties of N-Heteroaromatics. LX. Oxidation of Oxyhemoglobin by the Pesence of Phenothiazine Tranquilizers : Formation of Methemoglobin and Its Mechanism
Studies were made on the oxidation of oxyhemoglobin (HbO2) by the presence of phenothiazine system tranquilizers. Methemoglobin (MHb) was formed when a salt of ethopropazine (I), promethazine (II), promazine (III), or perazine (VI) was incubated with a suspension of human erythrocytes or with HbO2 solution obtained through hemolysis of this suspension. In either of the experiments with erythrocytes and HbO2 solution, the MHb-forming effect of the compound decreased in the order of I, II, III and VI. The HbO2-oxidizing activity of these derivatives was enhanced when they were photoirradiated before mixing of the derivatives with HbO2 solution. Chlorpromazine, methoxypromazine, thioperazine, fluphenazine, trimeprazine and methotrimeprazine formed MHb when their acid solutions were photoirradiated before their incubation with HbO2 solution. The HbO2-oxidizing activity of phenothiazine derivatives was also enhanced when they were subjected to potentiostatic electrolysis or pyrolysis. The amount of MHb formed in the incubation mixture paralleled the amount of semiquinone free radicals produced from the derivatives. On the basis of the results of comparative examinations on the HbO2-oxidizing activity, spectral change in the UV and visible regions, and polarographic half-wave potentials of the derivatives, it was presumed that, in the case where untreated phenothiazine derivatives were involved, cation radicals produced by some oxidizing substance in the incubation mixture played an important role in the formation of MHb from HbO2.