Interaction of phenothiazine drugs with human ceruloplasmin. Relation between activation of catecholamine neurotransmitter oxidation and electron donating ability of phenothiazine drugs.

The influence has been studied of 11 phenothiazine drugs on the oxidation of the catecholamine neurotransmitters noradrenaline and dopamine, catalyzed by human ceruloplasmin. The phenothiazine drugs were not transformed by the enzyme. This makes participation of free phenothiazine radical cations in the oxidation of the catecholamines unlikely. A relation between the electron donating capacity of the phenothiazine drugs and the activating effect on the enzyme has been observed. It is proposed that in the interaction of phenothiazine drugs with ceruloplasmin, charge transfer complexes between the phenothiazines and Cu2+ of the enzyme, are involved. The possible relevance of charge transfer complexes as a model for the receptor interactions of phenothiazine drugs is discussed.