RESUMO
Artemether (AM), a highly effective treatment for multidrug-resistant malaria and a component of artemisinin combination therapy, has been associated with some neurotoxicity following repeated high doses. This study was aimed at investigating the effect of AM on pentobarbitone sleep and electrical activities in rats. Wistar rats received AM i.p. at 3 dose levels: 1.5, 7.5, and 15 mg/kg, whereas control rats received 0.2 mL of the vehicle (3% v/v Tween 80). AM administered 20 min before pentobarbitone had no significant effect on the onset and duration of sleep. However, after a 7-day pretreatment, AM dose-dependently prolonged pentobarbitone sleep, as did chloramphenicol. Electroencephalogram and electromyogram recordings 20 min after pretreatment showed that AM (15 mg/kg) exhibited inhibitory activity similar to chlorpromazine as opposed to the excitatory effect of amphetamine. When pretreated for 7 days, rats receiving 1.5 mg/kg AM also showed inhibitory activity of the cortical centres, whereas desynchronization of the optic tectum and reticular formation was observed in rats pretreated with 7.5 and 15 mg/kg AM. The present data suggest that although the therapeutic equivalent dose of 1.5 mg/kg AM had no appreciable effects on pentobarbitone sleep but caused reduced electrical activity in rats, higher doses have more profound effects on both indices.
Assuntos
Artemisininas/farmacologia , Pentobarbital/farmacologia , Sono/efeitos dos fármacos , Anfetamina/farmacologia , Animais , Antimaláricos/administração & dosagem , Antimaláricos/farmacologia , Antipsicóticos/farmacologia , Artemeter , Artemisininas/administração & dosagem , Estimulantes do Sistema Nervoso Central/farmacologia , Cloranfenicol/análogos & derivados , Cloranfenicol/farmacologia , Clorpromazina/farmacologia , Sincronização Cortical/métodos , Relação Dose-Resposta a Droga , Eletromiografia/métodos , Feminino , Hipnóticos e Sedativos/farmacologia , Injeções Intraperitoneais , Masculino , Fenobarbital/farmacologia , Ratos , Ratos Wistar , Formação Reticular/efeitos dos fármacos , Formação Reticular/fisiologia , Sono/fisiologia , Colículos Superiores/efeitos dos fármacos , Colículos Superiores/fisiologia , Fatores de TempoRESUMO
Artemether, highly effective in multi-drug-resistant malaria is not routinely available for use in pregnancy due to the lack of adequate research data in animals and man. This study was therefore aimed at investigating some pregnancy-related effects of artemether. Artemether (1.5, 7.5 and 15 mg/kg i.p. daily for 7 days) did not produce changes in rat oestrous cycle. The drug did not prevent or prolong the rate of conception or parturition, cause pre-term delivery and affect litter size. Birth weight and growth rate of pups from artemether-pretreated dams were within the normal range. Artemether (48-480 microg/ml) had no agonist effect on the isolated uterine smooth muscles of both non-pregnant and pregnant rats and guinea pigs. However, the drug (24- 240 microg/ml) reduced oxytocin-induced contraction of uterine tissues concentration-dependently, particularly in pregnant uteri.
