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D M Chambers

Publications and source records attributed to D M Chambers.

22 records · Page 2Linked to original sources
PubMed1978

Halothane-induced sleeping time in the mouse: its modification by benzodiazepines.

The conditions under which prolongation of halothane-induced sleeping time in the mouse may be used as a test for centrally acting drugs are described. The test can be recommended for its practical advantages over methods using barbiturates to induce hypnosis; due cognizance must be taken of a diurnal variation in the response of mice to halothane. To assess the usefulness of the test the effects of amphetamine, chlorpromazine, histamine, morphine, nikethamide, pentobarbitone and SKF 525A have been investigated. The interaction between 5 benzodiazepines and halothane has been studied in particular. Results from sleeping time experiments, measurements of body temperature and of brain halothane concentrations suggest that the halothane-benzodiazepine interaction is due to additive CNS depressant effects. It was found that nitrazepam and diazepam were clearly more potent than chlorodiazepoxide, medazepam and oxazepam in respect of their interactions with halothane.

Animals↗
PubMed1977

Some observations on the mechanism of benzodiazepine-barbiturate interactions in the mouse.

1 The prolongation of pentobarbitone sleeping by five benzodiazepines, administered by prior intraperitoneal injection, was measured in mice. The pentobarbitone was injected either intraperitoneally or intracerebroventricularly. For each benzodiazepine, the prolongation was dose-related and differences in potency between benzodiazepines were not marked. 2 The percentage prolongation of sleeping times produced by most of the benzodiazepines was greater when the pentobarbitone was given intracerebroventricularly and was explained by a preferential addition of CNS depressant effects associated with this route. 3 To test whether the action of intraperitoneally administered pentobarbitone had been influenced by a metabolic component, the effects of nitrazepam on drug metabolism, measured by changes in plasma phenazone levels in the mouse, were studied. Nitrazepam (32 mg/kg, i.p.) produced a 23% reduction in the rate of phenazone metabolism. 4 Nitrazepam was also shown to have produced a transient fall in body temperature. Calculations based on Q10 values suggested that this hypothermia accounted, at most, for half the metabolic change measured.

Animals↗