Inactivation of cholinesterase induced by chlorpromazine cation radicals.

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Muraoka S, Miura T

Inactivation of cholinesterase induced by chlorpromazine cation radicals.

Pharmacol Toxicol. 2003 Feb;92(2):100-4.

PubMed ID

12747580 [ View in PubMed

]

Abstract

To clarify the mechanism of the side effect of chlorpromazine, we examined the inactivation of cholinesterase induced by chlorpromazine. Cholinesterase was inactivated and its activity was lost in rat serum during interaction of chlorpromazine with horseradish peroxidase and H2O2. When chlorpromazine was oxidized by horseradish peroxidase and H2O2, the reaction solution colored pink and the visible absorption spectrum was consistent with the absorption spectrum of the chlorpromazine cation radical (CPZ*+). Adding cholinesterase immediately decreased the pink color of CPZ*+, indicating that CPZ*+ directly attacked cholinesterase to cause loss of the enzyme activity. Tryptophan residues in cholinesterase sharply decreased during the interaction of cholinesterase with horseradish peroxidase and H2O2. Presumably, loss of tryptophan residues changed the conformation of the cholinesterase protein and then the activity of the enzyme was lost. Other phenothiazine derivatives, including promethazine, triflupromazine, trifluoperazine, trimeprazine, thioridazine and perphenazine, also inactivated cholinesterase during the oxidation by horseradish peroxidase and H2O2. These results suggest that phenothiazine cation radicals participate in toxicological signs caused by the drugs.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Chlorpromazine	Cholinesterase	Protein	Humans	Unknown	Inhibitor	Details
Triflupromazine	Cholinesterase	Protein	Humans	Unknown	Inhibitor	Details