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1. |
14C‐Antipyrine as a Model Compound in the Study of Drug Oxidation and Enzyme Induction in Individual Surviving Rats |
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Acta Pharmacologica et Toxicologica,
Volume 35,
Issue 2,
1974,
Page 91-97
Olav M. Bakke,
Michael Bending,
Jarle Aarbakke,
Donald S. Davies,
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摘要:
A rapid method for the estimation of antipyrine‐N‐methyl‐14C in small samples of whole blood has been developed. A study of the metabolite pattern in the urine of rats given this compound confirmed the overall importance of oxidative mechanisms in the metabolism of antipyrine. None of the metabolites interfered with the estimation of14C‐antipyrine in plasma. Applied to the determination of antipyrine in liver perfusate the present method compared favourably with the widely used spectrophotometric method. The mean half‐life of antipyrine in male Wistar rats was 88 min. with inter‐individual values in the range of 63‐128 min. The intra‐individual variation, as judged by the half‐lives found on 2 occasions, was considerably smaller. A brief course of phenobarbital treatment resulted in a significant shortening of the half‐life of antipyrine in all of the individual rats. These findings suggest that the determination of the half‐life of14C‐antipyrine in individual rats using the animals as their own controls, is a useful experimental tool for the study of factors which i
ISSN:0001-6683
DOI:10.1111/j.1600-0773.1974.tb00728.x
出版商:Blackwell Publishing Ltd
年代:1974
数据来源: WILEY
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2. |
The Biotransformation of Cyclophosphamide in Man: Analysis of the Variation in Normal Subjects |
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Acta Pharmacologica et Toxicologica,
Volume 35,
Issue 2,
1974,
Page 98-106
H. T. Mouridsen,
O. Faber,
L. Skovsted,
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摘要:
The metabolism of cyclophosphamide was studied in 40 subjects aged 33‐84, mean 64 years. After the intravenous injection of14C‐cyclophosphamide the radioactivity of the plasma and urine samples was analysed as regards unchanged cyclophosphamide and its metabolites. The parameters of the metabolism, half‐life of cyclophosphamide in the serum, peak and integrated serum concentration of the metabolites, distribution volume of injected radioactivity and the rate of excretion of cyclophosphamide and metabolites in the urine all exhibited a very large interindividual variation of a factor of 3‐10. Spontaneous intra‐individual variation, however, studied in 9 subjects, did not exceed that due to inaccuracy of the analysis. The possible clinical implications of these results are
ISSN:0001-6683
DOI:10.1111/j.1600-0773.1974.tb00729.x
出版商:Blackwell Publishing Ltd
年代:1974
数据来源: WILEY
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3. |
Interactions Between Salicylic Acid and Pyridy;‐3‐methanol: Anti‐inflammatory and Teratogenic Effects |
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Acta Pharmacologica et Toxicologica,
Volume 35,
Issue 2,
1974,
Page 107-118
E. Cekanova,
K. S. Larsson,
E. Mörck,
G. Åberg,
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摘要:
Anti‐inflammatory and teratogenic effects of nicotinic acid, pyridyl‐3‐methanol and salicylic acid were studied. Tests were also performed on mixtures of salicylic acid and pyridyl‐3‐methanol and on an ester of pyridyl‐3‐methanol and salicylic acid (S‐2063). Anti‐inflammatory effects were studied on carrageenin‐in‐duced rat paw oedema and stabilizing effects were studied on rat liver lysosomes. Teratological studies were carried out on NMRI mice.Nicotinic acidwas found to be very potent in the anti‐inflammatory test and in stabilizing rat liver lysosomes.Pyridyl‐3‐methanolhad less marked anti‐inflammatory effects and had no significant stabilizing effect on the lysosomes. No foetal damage was caused.Salicylic acidhad anti‐inflammatory effects that were even less marked than those of pyridyl‐3‐metha‐nol, but had slight stabilizing effects on the lysosomal membranes. Salicylate‐induced skeletal malformations were obtained after treatment in early organogenesis. Given during late pregnancy a high incidence of foetal death and premature birth was observed.S‐2063had anti‐inflammatory effects that were approximately the same as that of an equimolar mixture of salicylic acid and pyridyl‐3‐methanol. S‐2063 caused a decreased membrane permeability of the lysosomal membranes for β‐glu‐curonidase but not for acid phosphatases. The teratogenic effect was not much increased as could be expected
ISSN:0001-6683
DOI:10.1111/j.1600-0773.1974.tb00730.x
出版商:Blackwell Publishing Ltd
年代:1974
数据来源: WILEY
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4. |
Studies on the Interaction of Reserpine, d‐Amphetamine, Apomorphine and 5‐Hydroxytryptophan |
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Acta Pharmacologica et Toxicologica,
Volume 35,
Issue 2,
1974,
Page 119-130
Christopher Goetz,
Harold L. Klawans,
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摘要:
The effect of reserpine on dopamine related d‐amphetamine and apomorphine‐induced stereotyped behaviors and serotonin related myoclonic behaviour was studied. Reserpine pretreatment potentiated amphetamine‐induced stereotyped behaviour, apomorphine‐induced stereotyped behaviour and 5‐hydroxytryptophan‐induced myoclonic behaviour. The possibility that this was related to the influence of reserpine on the behaviourally active monoamine pools was discussed. 5‐Hydroxy‐tryptophan in small amounts was found to inhibit amphetamine‐induced stereotyped behaviour in reserpine pretreated guinea pigs. d‐Amphetamine appeared to potentiate 5‐hydroxytryptophan myoclonic behaviour and this potentiation was further increased by reserpine. 5‐Hydroxytryptophan did not inhibit apomorphine‐induced stereotyped behaviour in reserpinized animals. These results are discussed in relation to the influence of reserpine on the balance of active neurotran
ISSN:0001-6683
DOI:10.1111/j.1600-0773.1974.tb00731.x
出版商:Blackwell Publishing Ltd
年代:1974
数据来源: WILEY
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5. |
Withdrawal in the Rat after Long‐term Forced Oral Barbital Administration |
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Acta Pharmacologica et Toxicologica,
Volume 35,
Issue 2,
1974,
Page 131-144
Göran Wahlström,
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摘要:
In 5 experiments a barbital solution was the sole drinking source for male rats. On an average 200 mg/kg/day was consumed. There was no increase in dosage during treatments between 12 and 42 weeks. A positive correlation between the dose of barbital consumed and a pre‐experimental hexobarbital threshold developed during the treatment (fig. 5). After the end of the barbital treatment the animals showed a loss of weight and an increased water consumption. Tolerance recorded as an increase in the hexobarbital threshold had a first maximum 3 days after the end of the barbital treatment. After prolonged barbital treatment a second maximum was seen approximately 3 weeks later. Using the duration of barbital treatment as an independent variable, none of these changes in the abstinence period after barbital treatment showed a tendency towards a steady state (fig. 6
ISSN:0001-6683
DOI:10.1111/j.1600-0773.1974.tb00732.x
出版商:Blackwell Publishing Ltd
年代:1974
数据来源: WILEY
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6. |
Effects of Ethyleneglycol Dinitrate and Related Compounds on Ethanol Preference and Ethanol Metabolism |
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Acta Pharmacologica et Toxicologica,
Volume 35,
Issue 2,
1974,
Page 145-154
Setsuo Komura,
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摘要:
Ethanol preference in rats (ALKO strains) was studied by injecting ethyleneglycol dinitrate, glyceryl trinitrate, propyleneglycol dinitrate and ethyleneglycol mononitrate. Their effects on ethanol metabolism and on the activities of liver alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (AldDH) were also examined. All four compounds caused a marked decrease in ethanol preference. When administered 30 minutes before the injection of ethanol, all four drugs significantly delayed the disappearance of ethanol and acetaldehyde from the blood. With 150 mg/kg b.wt. of ethyleneglycol dinitrate, the blood acetaldehyde level reached 770 nmol/ml one hour after ethanol (2 g/kg b.wt.) injection. This contrasted with 30 nmol/ml for the control. Similar results were obtained with the other compounds. 3 hours after the administration of 150 mg/kg of nitrate, the liver ADH activities were inhibited by 21‐46% and the liver Ald DH activities by 32‐60%. These findings suggest that the decrease in ethanol preference and the inhibition of ethanol and acetaldehyde elimination are closely related to the decrease in liver ADH and AldDH activities in the presence of these four organic nitra
ISSN:0001-6683
DOI:10.1111/j.1600-0773.1974.tb00733.x
出版商:Blackwell Publishing Ltd
年代:1974
数据来源: WILEY
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7. |
Hepatic Tryptophan Oxygenase Activity as a Marker of Changes in Protein Metabolism during Chronic Ethanol Treatment |
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Acta Pharmacologica et Toxicologica,
Volume 35,
Issue 2,
1974,
Page 155-168
Jørg Mørland,
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摘要:
Rats were given ethanol daily to provide 22, 30 or 38 per cent of the total calories consumed. Sucrose substituted ethanol isocalorically in the respective control groups. The two diets providing the largest amount of ethanol caused a significant reduction of hepatic tryptophan oxygenase, TO, activity, which occurred after 7 days (38 per cent of the calories as ethanol), or after 21 days (30 per cent of the calories as ethanol). The reduction of enzyme activity persisted throughout the remainder of the experimental period. Hepatic triglycerides, plasma lipids, plasma enzymes (alkaline phosphatase, GOT and GPT) and hepatic histology was only slightly or transiently affected during the period of ethanol treatment. The reduction of TO‐activity was accompanied by reduced dexamethasone induction of TO and tyrosine aminotransferase, TAT, during liver perfusion. The incorporation of labelled amino acids into hepatic protein was reduced in perfused livers and alsoin vivowhen TO‐activity was decreased. It was concluded that the activity of tryptophan oxygenase was most probably an indicator of the synthesis of this enzyme and other proteins sensitive to the chronic administration of etha
ISSN:0001-6683
DOI:10.1111/j.1600-0773.1974.tb00734.x
出版商:Blackwell Publishing Ltd
年代:1974
数据来源: WILEY
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