Summary
Hepatic microsomal enzyme systems can be activated by pretreatment with phenobarbital, other barbiturates, ddt, and many other drugs. Contrarily, another compound such as skf 525-a, ethionine, and puromycin can inhibit the same enzymatic mechanisms.
The sleep-time periods of albino rats produced by pentobarbital, thiopental, zoxazolamine, ci-581, diazepam, and gamma-hydroxybutyrate were significantly shortened by previous administration of phenobarbital twice daily for four days. However, the duration of action of the same anaesthetics was significantly prolonged when the animals were “pretreated” by the administration of skf 525-a, an inhibiter of liver microsomal enzymes.
Résumé
Des groupes de dix rats chacun ont reçu en injections intrapéritonéales des médicaments employés en pratique anesthésique comme sédatifs ou comme agents anesthésiques par voie endoveineuse. Nous avons déterminé la durée du sommeil par la présence ou ľabsence du “réflexe à se lever.” Un certain nombre ďanimaux ont été traités ďabord durant quatre jours par des injections, deux fois par jour, ďune quantité de phénobarbital 30 mg/kg et ce n’est que le cinquième jour que ľagent anesthésique a été injecté. Dans tous les groupes, nous avons observé une diminution importante de la durée des périodes de sommeil. Par contre, les rats qui avaient reçu 100 mg/kg de beta-diéthylaminoéthyl diphénylpropylacétate (skf 525-a) ont connu une prolongation de leurs périodes de sommeil.
Un traitement préalable au phénobarbital et au skf 525-a a démontré que ces médicaments pouvaient respectivement augmenter et diminuer ľactivité des enzymes hépatiques microsomales, probablement par prolifération du réticulum lisse endoplasmique des hépatocytes. Les médicaments que nous avons étudies sont le pentobarbital, le thiopental, le Ketalar® (ci-581), le diazepam, le gamma hydroxybutyrate et le myorésolutif zoxazolamine qui, jusqu’à un certain point, est métabolisé par le foie et partiellement éliminé comme glucuronides. Le glucuronyl transferase, une enzyme impliquée dans le dernier processus, peut être soit activée soit inhibée par un traitement au préalable au phénobarbital ou au skf 525-a respectivement.
Ľintéraction des médicaments, par effet sur les systèmes hépatiques ďenzyme microsomal peut être responsable de certains cas de “tolérance” ou de “sensibilité” à certains agents anesthésiques par voie endoveineuse.
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This study was supported by US Public Health Service grant fr 05357-08 to the University of Colorado Medical Center.
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Piel, M.T., Aldrete, J.A. & Jones, G. Influence of enzyme induction on the sleeping time of rats. Can. Anaes. Soc. J. 16, 538–546 (1969). https://doi.org/10.1007/BF03004547
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DOI: https://doi.org/10.1007/BF03004547