RESUMO
An increase in stereotyped behavior was observed in rats injected daily with cocaine (40 mg/kg, IP), as compared with the first day. This increase persisted 14 days after discontinuation of the drug treatment, and corresponded to increased levels of 3H-cocaine norcocaine and benzoylecgonine in brain. Pretreatment of the animals with SKF-522A, an inhibitor of cocaine demethylation, produced a decrease in stereotypy rating and concomitantly a lower level of 3H-norcocaine in the brain. The role of this metabolite in the production of cocaine-induced stereotyped behavior is discussed.
Assuntos
Comportamento/efeitos dos fármacos , Cocaína/metabolismo , Comportamento Estereotipado/efeitos dos fármacos , Animais , Química Encefálica/efeitos dos fármacos , Cocaína/antagonistas & inibidores , Cocaína/farmacologia , Feminino , Humanos , Proadifeno/farmacologia , Ratos , Fatores de TempoRESUMO
In vitro and in vivo studies in rats indicate cocaine to be metabolized primarily in the liver to form benzoylecgonine and norcocaine. The formation of these metabolites was significantly hindered by SKF-525A, a microsomal enzyme inhibitor. In in vivo studies, pretreatment of rats with SKF-525A prior to receiving cocaine resulted in increased amounts of unchanged cocaine in the brain. No accompanying increase in spontaneous motor activity was observed for these animals, indicating a possible role for metabolites in the stimulant action of cocaine.
Assuntos
Cocaína/metabolismo , Proadifeno/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cocaína/sangue , Depressão Química , Hidrólise , Técnicas In Vitro , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Atividade Motora/efeitos dos fármacos , RatosRESUMO
Hydrolysis of 14C-cocaine in human serum, separation of the metabolites on TLC, and subsequent identification on GLC is described. AT 1 H, 20 percent of the cocaine was metabolized to benzoylecgonine, ecgonine and ecgonine methylester. At this time interval the highest percent of product was in the form of the ecogonine methyl ester, a metabolite not previously reported in humans. After 4 h, 67 percent of the cocaine was hydrolyzed; of this, 45 percent was benzoylecgonine and ecgonine in a ratio of 1.6 to 1. The half-life for cocaine hydrolyzed in human serum was approximately 2.5 h.
Assuntos
Cocaína/sangue , Cocaína/análogos & derivados , Meia-Vida , Humanos , Hidrólise , Técnicas In Vitro , Fatores de TempoRESUMO
Norcocaine was prepared from cocaine utilizing diethyl azodicarboxylate. The rate of demethylation of 14C-cocaine in rats receiving either chronic or acute dosages of the drug was investigated. No significant difference in the rate of 14CO2 exhalation from the two groups was observed.
