Life sciences
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To assess whether the anesthetic and anticonvulsant activities of alphaxalone display diurnal variability, groups of Syrian hamsters were studied at 4 h-intervals during a 24 h-cycle. The administration of alphaxalone (5 mg/kg) brought about a greater anesthetic activity (loss of righting reflex) at the middle of the photophase. When assessed in hamsters injected with 3-mercaptopropionic acid, alphaxalone displayed maximal anticonvulsant activity at the 4th of darkness. Evaluation of the time needed for first convulsive response indicated that alphaxalone did not show time-dependent effects, while in control hamsters seizure threshold was low during daylight and attained maximal values at night, showing a peak in seizure threshold at light-dark transition.
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Comparative Study
Comparative behavioral pharmacology and toxicology of cocaine and its ethanol-derived metabolite, cocaine ethyl-ester (cocaethylene).
The present study compared the behavioral and toxic effects of cocaine and its ethanol derived metabolite, cocaine ethyl-ester (cocaethylene). Both drugs produced qualitatively similar psychomotor stimulant effects. Cocaine and cocaethylene increased locomotor activity in mice, with cocaine approximately four times more potent than cocaethylene. ⋯ In rats and squirrel monkeys trained to discriminate cocaine injections from saline, cocaine was approximately three to five times more potent than cocaethylene in producing these cocaine-like interoceptive effects. In contrast to the behavioral effects, cocaine and cocaethylene were equipotent in producing convulsions, and cocaethylene was more potent than cocaine in producing lethality. These results suggest that the conversion of cocaine to cocaethylene with simultaneous cocaine and alcohol use may produce an increased risk of toxicity due to a decrease in the potency of cocaethylene in producing psychomotor stimulant effects, and its increased potency in producing toxicity.