RESUMO
Antioxidants and disulphide bond reducing agents have shown the central N-cholinolytic effect and prevented nicotinic-induced contraction of isolated smooth muscle preparation (ISMP). N-cholinolytic pediphen and antioxidant ionol reduced disulphide bond in the supernatant of mouse brain, but sulphydryl-oxidant agents 5'5-Dithiobis (2-nitrobenzoic acid) abolished N-cholinolytic effect of pediphen on ISMP. It is concluded that reduction of disulphide bond of N-cholinoceptor is a molecular mechanism of its blockade.
Assuntos
Hidroxitolueno Butilado/farmacologia , Neurônios/efeitos dos fármacos , Nicotina , Receptores Colinérgicos/efeitos dos fármacos , Simpatolíticos/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dissulfetos/metabolismo , Técnicas In Vitro , Camundongos , Contração Muscular , Músculo Liso/efeitos dos fármacos , Nicotina/antagonistas & inibidores , Ratos , Receptores Colinérgicos/metabolismo , EspectrofotometriaRESUMO
It was found therapeutic-preventive effectiveness of antioxidants (1,4-dihydropyridine derivatives) at poisoning with malathion insecticide. The effect of 1,4-dihydropyridine derivatives can be attributed to a prevention of lipid peroxidation. Antioxidants do not affect the toxicity of 0,0-dimethyl-0-2,2-dichlorvinylphosphate. Thus, antioxidants are pathogenetic drugs for treatment of poisonings with cholinesterase inhibitors.
Assuntos
Antioxidantes/farmacologia , Inibidores da Colinesterase/intoxicação , Animais , Antioxidantes/uso terapêutico , Di-Hidropiridinas/farmacologia , Di-Hidropiridinas/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Malation/intoxicação , Masculino , Camundongos , RatosRESUMO
The effect of central M- and N-cholinolytics on Fe++-ascorbate-dependent lipid peroxidation (LP) in the rat brain homogenate was studied in vitro. Central N-cholinolytics were shown to inhibit LP. Pediphen was the most active drug. Central M-cholinolytics were not active. Pediphen and an antioxidant ionol equally decreased LP in the rat brain after carbon tetrachloride intoxication (3 ml/kg). Ionol and pediphen had N- and not M-cholinolytic effect. It is suggested that membrane stabilization by N-cholinolytics is dependent on the antioxidant effect of the drugs. These data show an important role of LP in the function of cholinergic system.