title: The inhibition of lipid peroxidation by cinnarizine. Possible implications to its therapeutic and side-effects.
abstract: Cinnarizine has antivasoconstrictor properties and improves red-cell deformability. Its major side-effects are the induction of extrapyramidal reactions. It is a calcium antagonist, but it was suggested that its effects may depend on other mechanisms, namely on antiperoxidant properties. We have studied these properties in different biological systems, intact red-cells included. The occurrence of lipid peroxidation was determined by the formation of 2-thiobarbituric acid reactive products. Cinnarizine was found to inhibit spontaneous lipid peroxidation in rat liver homogenates, copper-induced lipid peroxidation in human plasma and copper-induced and hydrogen peroxide-induced lipid peroxidation in human red-cells. In red-cells, the inhibition of lipid peroxidation is accompanied by the inhibition of hemolysis. Copper-induced red-cell lipid peroxidation is 85% inhibited by as little as 5 microM cinnarizine. The antioxidant activity of cinnarizine may contribute to explain some of the effects of this drug.
authors.affiliation: Instituto de Química Fisológica, Faculdade de Medicina, Lisboa, Portugal.
authors.forename: A C
authors.initials: AC
authors.lastname: Fernandes
authors.forename: P M
authors.initials: PM
authors.lastname: Filipe
authors.forename: H
authors.initials: H
authors.lastname: Coelho
authors.forename: C F
authors.initials: CF
authors.lastname: Manso
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002936:Cinnarizine / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013858:Thiobarbiturates / Q000378:metabolism
chemical_list: D000975:Antioxidants; D013858:Thiobarbiturates; D002936:Cinnarizine; D003300:Copper; D006861:Hydrogen Peroxide; C029684:thiobarbituric acid