Induced increase of meprobamate metabolism in rats pretreated with phenobarbital or phenaglycodol in relation to age

Kato, Ryo; Chiesara, E.; Frontino, G.

doi:10.1007/bf02158634

Cited by 18 publications

(7 citation statements)

References 2 publications

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“…More over, it was observed that the induction of microsomal drug-metabolizing enzymes by phenobarbital was more effective in young rats than in old rats (4,5).In the present communication, we wish to report the evidence that, in contrast to the results obtained with rats, clear age difference was not observed in the activity of drug-metabolizing enzymes in mice and there was no clear age difference in the induc tion of drug-metabolizing enzymes by phenobarbital. …”

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confidence: 62%

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Studies on Age Difference in Mice for the Activity of Drug-Metabolizing Enzymes of Liver Microsomes

Kato

Takanaka

Onoda

1970

Japanese Journal of Pharmacology

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In previous papers, we reported that the activity of drug-metabolizing enzymes was higher in young female rats than in old female rats and that the duration of hexo barbital anesthesia was shorter in the young females than in the old females (1-3). More over, it was observed that the induction of microsomal drug-metabolizing enzymes by phenobarbital was more effective in young rats than in old rats (4,5).In the present communication, we wish to report the evidence that, in contrast to the results obtained with rats, clear age difference was not observed in the activity of drug-metabolizing enzymes in mice and there was no clear age difference in the induc tion of drug-metabolizing enzymes by phenobarbital. MATERIALS AND METHODSMale mice of ICR strain were used, unless otherwise specified. Phenobarbital (80 mg/kg) was given intraperitoneally 48 and 24 hours before sacrifice. Pooled liver from 3 mice was used for the preparation of each homogenate. Preparation of post mitochondrial and microsomal fractions was carried out as described in a previous paper (6). The activity of drug-metabolizing enzymes of liver microsomes was assayed as described in the previous paper (6). The hydroxylation of hexobarbital was determined by measuring the disappearance of the substrate according to the method of Cooper and Brodie (7). The N-demethylation of aminopyrine was determined by the forma tion of 4-aminoantipyrine (La Du et al.) (8). The hydroxylation of aniline was deter mined by the formation of p-aminophenol according to the method described by Kato and Gillette (9). The nitroreduction of p-nitrobenzoic acid was determined by measur ing the p-aminobenzoic acid formed according to the method of Fouts and Brodie (10). NADPH-cytochrome c reductase was determined according to the method of Williams and Kamin (11). NADPH-neotetrazolium reductase was assayed as described in the previous paper (2). The contents of microsomal protein and cytochrome P-450 were determined by the method of Lowry et al. (12) and Omura and Sato (13), respective ly. The duration of hexobarbital anesthesia and zoxazolamine paralysis was determined by the loss of the righting reflex. Strychnine toxicity was evaluated by the convulsion rate and mortality.

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confidence: 62%

“…over, it was observed that the induction of microsomal drug-metabolizing enzymes by phenobarbital was more effective in young rats than in old rats (4,5).…”

mentioning

confidence: 99%

Studies on Age Difference in Mice for the Activity of Drug-Metabolizing Enzymes of Liver Microsomes

Kato

Takanaka

Onoda

1970

Japanese Journal of Pharmacology

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“…Further supports for this view were obtained from the studies on the toxicities of strychnine and OMPA that the toxicity of strychnine was increased in the old rats, while the toxicity of OMPA was decreased. The toxicities of strychnine and OMPA are closely related to the activities of drug-metabolizing enzymes and when the enzyme activities are decreased the toxicity of strychnine is increased (8,13), whereas the toxicity of OMPA is decreased (8,11,12).…”

Section: Discussionmentioning

confidence: 99%

“…6. Effect of phenobarbital treatment on the duration of hexobarbital narcosis in different aged female rats In previous papers it was observed that the effects of phenobarbital to increase in the activities of microsomal drug-metabolizing enzymes and NADPH-electron transport system were decreased with the increase in age and in the old rats significant increase of the ac tivities by phenobarbital was not observed any more (13,14).…”

Section: Figmentioning

confidence: 94%

Metabolism of Drugs in Old Rats (Ii) Metabolism in Vivo and Effect of Drugs in Old Rats

Kato

Takanaka

1968

Japanese Journal of Pharmacology

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It is well known that the effects of some drugs in old animals quite differ from those in young animals. For example, Farner and Verzar (1) observed that the action of am phetamine to increase moter activity was more marked in young rats than in old rats and the action of hexobarbital to antagonized against the amphetamine action was more ef fective in old rats than in young rats. Moreover, the duration of hexobarbital anesthesia was longer in old rats than in young rats (2). Similarly, Petty and Karler (3) observed that anticonvulsive activity of acetazolamide and phenobarbital was more marked in old rats than in young rats.However, there is no study on the mechanism of such altered drug response in rela tion to the rate of drug metabolism. In a previous paper it was reported from our labo ratory that the activities in the oxidation and reduction of drugs and NADPH-linked elec tron transport system in liver microsomes of male and female rats were progressively decreased with aging (4).It is, therefore, of interest to investigate whether or not the metabolism in vivo of vari ous drugs is decreased in old rats in accordance with the decrease in the metabolic activi ties of liver microsomes observed in the in vitro experiments. Moreover, the relationship between the effects of drugs and the rate of in vivo metabolism of drugs in the old rats was studied. MATERIALS AND METHODSMale and female rats of Wistar strain of about 40, 100, 300 and 600 days old were used . In most of experiments, 100 days old rats (young rats) and 600 days old rats (old rats) were used.Pentobarbital sodium, hexobarbital sodium, strychnine sulphate and OMPA (octa methylpyrophosphoramide) were dissolved in distilled water and carisoprodol was sus pended with 1 % solution of sodium carboxymethylcellulose and all drugs were given intraperitoneally.The preparation of microsomes and the determinations of pentobarbital and cariso prodol oxidation were carried out according to the methods described in a previous paper (4). The metabolism in vivo of carisoprodol and pentobarbital were determined by the rate of disappearance of the drugs in the serum and brain after intraperitoneal injection .

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“…It is well known that octamethylpyrophosphoramide itself has no anticholinesterase activity, but that it must be acted upon by the liver before exerting its toxic effects. Ethionine inhibited the inductive effects of both phenobarbital and phenaglycodol on the metabolism of pentobarbital and meprobamate (100,101,102,107) . This drug-induced increase in metabolic activity, which was maximal 48 hours after treatment, was inhibited by the coadministration of ethionine.…”

Section: Shideman and Manneringmentioning

confidence: 94%

Metabolic Fate

Shideman¹,

Mannering²

1963

Annu. Rev. Pharmacol.

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1 The survey of the literature pertaining to this review was concluded in May 1962.2 Abbreviations used in this chapter include: ADH (alcohol dehydrogenase); AT (3-amino-l,2,4-triazole); CoA (coenzyme A); NAD (nicotinamide-adenine dinucleotide); NADH2 (nicotinamide-adenine dinucleotide reduced form); NADP (nicotinamide-adenine dinucleotide phosphate); NADPH2 (nicotinamide-adenine dinucleotide phosphate reduced form); TEPA (triethylenephosphoramide).

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Induced increase of meprobamate metabolism in rats pretreated with phenobarbital or phenaglycodol in relation to age

Cited by 18 publications

References 2 publications

Studies on Age Difference in Mice for the Activity of Drug-Metabolizing Enzymes of Liver Microsomes

Studies on Age Difference in Mice for the Activity of Drug-Metabolizing Enzymes of Liver Microsomes

Metabolism of Drugs in Old Rats (Ii) Metabolism in Vivo and Effect of Drugs in Old Rats

Metabolic Fate

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