title: The antioxidant activity of caroverine.
abstract: Caroverine, 1-(2-diethylaminoethyl)-3-(p-methoxy benzyl)-1,2-dihydro-2-quinoxalin-2-on-hydrochloride, is a class B calcium-channel-blocker and antiglutamatergic agent with significant effects on the brain function. Caroverine exhibits competitive AMPA antagonism, and at higher concentrations, noncompetitive NMDA antagonism. In clinical practice caroverine is used as a spasmolytic and otoneuroprotective agent. Since reactive oxygen species are supposed to be involved in the pathogenesis of inner ear diseases in which caroverine shows beneficial effects, the present study aimed to investigate the antioxidant properties of caroverine. Lipid peroxidation of liposomal membranes was suppressed in the presence of caroverine. In order to understand the mechanism of this antioxidant action of caroverine, we determined the rate constants both for a possible reaction with superoxide (O(2)(.-)) radicals from xanthine/xanthine oxidase and for a possible reaction with hydroxyl (.OH) radicals in Fenton system. Using a defined chemical reaction model O(2)(.-) scavenging was found to occur at a rather low rate constant only (3 x 10(2)M(-1)s(-1)). Thus, a reaction of caroverine with O(2)(.-) radicals is of marginal significance. In contrast, the reaction of caroverine with .OH radicals occurs at an extremely high rate constant (k=1.9 x 10(10)M(-1)s(-1)). The strong antioxidant activity of caroverine is therefore based both on the partial prevention and highly active scavenging of hydroxyl radicals.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Veterinaerplatz 1, A-1210 Vienna, Austria.
authors.forename: Natalia
authors.initials: N
authors.lastname: Udilova
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kozlov
authors.forename: Werner
authors.initials: W
authors.lastname: Bieberschulte
authors.forename: Klemens
authors.initials: K
authors.lastname: Frei
authors.forename: Klaus
authors.initials: K
authors.lastname: Ehrenberger
authors.forename: Hans
authors.initials: H
authors.lastname: Nohl
mesh_terms: D000704:Analysis of Variance; D000975:Antioxidants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D013481:Superoxides; D014810:Vitamin E; D017665:Hydroxyl Radical; C000957:caroverine