Induction of microsomal drug-metabolizing enzymes caused by hexobarbital.

Hexobarbital was given to anaesthetized mice for a period of 7 h by repeated i. p. injection, first of 100 mg/kg,then several times of 50 mg/kg. A high level of hexobarbital was maintained in the liver. The activity of microsomal drug-metabolizing enzymes was induced by this treatment with hexobarbital. 30 min after a single i. p. injection of 100 mg/kg of hexobarbital, there was a significant inhibition of aminopyrine N-demethylase but none of cytochrome c and neotetrazolium reductases. Hexobarbital in vitro inhibits aminopyrine N-demethylase but not cytochrome c reductase.     

Decreased activities of liver microsomal drug-metabolizing enzymes in the rats bearing walker carcinosarcoma

Riassunto Ratti portatori di carcinosarcoma di Walker, presentano una notevole diminuzione di attività di quel gruppo di enzimi microsomici epatici da cui dipende il metabolismo di una numerosa serie di farmaci. I nostri rilievi sono stati fatti prendendo in considerazione il metabolismo dell'esobarbital, della stricnina e del meprobamato.     

Interaction of organic dyes with hepatic microsomal drug-metabolizing monoöxygenases in vitro

Summary Organic dyes such as malachite green, methylene blue, fuchsin, safranine T, neutral red, phenazine methosulphate, riboflavin, dichlorophenolindophenol, phenolphthalein, and fluorescein, inhibit hepatic microsomal mixedfunction oxidases and, partly, enhance, partly, inhibit hepatic microsomal NADPH-dependent cytochrome c and neotetrazolium reductases, in contrast to other inhibitors of drug metabolism which do not affect cytochrome c reductase but only interact with cytochrome P-450.Dedicated to Prof. G. Pfleiderer on the occasion of his 60th birthday.Acknowledgment. The author thanks Mrs Fey, Mrs Meier, and Mr Weinrauch, for their skilful technical assistance; he is grateful to Dr A. Sinharay (Hoechst AG) for providing him with anisic ester and methylayapanine.     

Effects of oral contraceptive steroids (norethisterone/mestranol) on the activities of hepatic drug-metabolizing enzymes in iron-deficient anemic rats

Either oral contraceptive steroid (norethisterone/mestranol; N/M) treatment or iron-deficiency (Fe(-] anemia alone caused an increase in NADPH cytochrome c reductase and in three hepatic microsomal mixed-function oxidase activities in female rats. When N/M treatment and the Fe(-) diet are combined, no further change in hepatic enzyme activity is seen compared with that with either treatment alone.     

Elevation of blood glucose and induction of hepatic enzymes by 2-deoxyglucose in mice with hypothalamic damage caused by gold thioglucose

Zusammenfassung 2-Deoxyglukose führt bei Mäusen zu Blutzuckersteigerung und in der Leber zu Aktivierung der Tryptophan-Pyrrolase und Tyrosine-Transaminase bei durch Goldthioglukose verursachten hypothalamischen Schäden.

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I thankHarold D. Snoddy andBetty J. Warren for expert technical assistance.     

Inhibition of liver microsomal epoxide hydrase by cyproheptadine epoxide

Summary Cyproheptadine epoxide is a competitive inhibitor or rat liver microsomal epoxide hydrase with an apparent K₁-value of 0.75 mM. Cyclobenzaprine and its epoxide stimulate in vitro the activity of this enzyme, whereas cyproheptadine, carbamazepine and carbamazepine epoxide have no effect.     

Diphasic action of the aliphatic amide,HOE 17879, on hepatic microsomal drug metabolizing enzymes in the mouse

Summary -Hydroxy--ethylbutyryl-diethylamide (HOE 17879) influences the hepatic microsomal drug hydroxylating enzyme system of mice in a two-phasic way: First it reduces the overall reaction of drug hydroxylation but not the single enzymes whilst in the second period it increases enzyme activities.Acknowledgments. The authors are indebted to their colleague, Dr.K. Schmitt, for making the substance HOE 17879 available. They wish to thank to Mr.Mayer, Mr.Paulusch Mrs.Fey, Mrs.Stein, and MissFehlings for their skilful assistance in the project.     

Inhibition of oxidizing enzymes by metronidazole

Zusammenfassung Eine unerwartete Möglichkeit, wie Metronidazol zu einer nur scheinbaren Hemmung der Alkoholdehydrogenase führen könnte, wird aufgedeckt.

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This research was supported in part by a grant from Ayerst Laboratories (New York), Scientific Advisory Board of the Licensed Beverage Industries (New York), and the Milheim Foundation for Cancer Research (Denver, Colorado). We thank Dr.T. Robitscher of Ayerst Laboratories and Dr.V. Drill of G. D. Searle & Co. for reagents used, and Dr.Drill for unpublished information from his laboratories.     

On the endocrine basis of sexual differences in hexobarbital sleeping-time in rats

Zusammenfassung Die Schlafdauer ist nach Hexobarbitalbehandlung bei weiblichen Ratten länger als bei männlichen. Durch Kastrierung wird sie bei männlichen Tieren verlängert, bei weiblichen verkürzt. Bei ovariektomierten Ratten wird sie durch Oestron verlängert. Testosteron-Propionat ist wirkungslos. Bei kastrierten männlichen Ratten wird sie dagegen durch Testosteron-Propionat verkürzt während Oestron keinen Einfluss hat.