ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb03516.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Following single intraperitoneal doses the halothane metabolites, trifluoroethanol (TFE) and trifluoroacetaldehyde hydrate (TFAIH), produced a marked dose‐dependent accumulation of fat in mouse liver, the maximal effect occuring at about 24 hours after administration. Slight fatty changes already occurred with non‐lethal doses, but repeated administration did not, however, cause necrosis of the liver cells. Electron microscopy suggested that part of the fat was composed of phospholipids, which are known to accumulate during energy loss. The glycogen granules almost completely disappeared in the liver, this being also confirmed by chemical determination. Trifluoroacetic acid (TFAA) not only caused slight fat accumulation, but also an increase in liver glycogen. In human fibroblast cell cultures TFAIH, even in small concentrations, and TFAA in high concentrations, inhibited cell growth. TFE did not affect the growth of the fibroblasts, probably because no enzymatic system is available in these cells to metabolize TFE to the toxic aldehyde. Two mechanisms may be responsible for the hepatotoxicity of TFE and TFAIH: a) formation of phospholipids due to energy requirement and b) accumulation of liver triglycerides due to blocking of e. g. transport enzy

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00578.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

After the administration ofp‐hydroxyamphetamine 20 mg/kg intraperitoneally, there was a 50 per cent decrease in the brain noradrenaline (NA) level and a 70 per cent decrease in the heart NA level at 4–8 hours after the injection. Control levels of brain and heart NA were reached at 96–144 hours after a single dose of the drug. Repeated injections ofp‐hydroxyamphetamine, 20 mg/kg twice daily for 3 days, caused a depletion of brain and heart NA to about 20 per cent of the control levels. The brain dopamine (DA) level was reduced to 85 per cent of the control level at 1 hour after 20 mg/kg of the drug and to 76 per cent after 40 mg/kg. After the repeated injections ofp‐OH‐A, the brain DA was reduced to 70 per cent of the control level. Radioactively labelledp‐hydroxynorephedrine was isolated from both brain and heart tissue extracts after the administration ofp‐hydroxyamphetamine‐3H. Parahydroxynorephedrine‐3H remained in the brain and the heart as long as the NA levels were decreased. The NA deficit in the brain and heart corresponded approximately to the amounts ofp‐hydroxynorephedrine‐3H present in the tissues. In reserpine pretreated rats the amounts ofp‐hydroxynorephedrine‐3H formed in the brain and heart tissues were reduced, indicating thatp‐hydroxynorephedrine is bound by a reserpine sensitive storage mechanism. Administration ofp‐hydroxyamphetamine or amphetamine accelerated the disappearance of labelledp‐hydroxynorephed

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00579.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb03283.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The brain and heart NA in rats was maximally decreased by 28–52% at 3–12 hours after 20 mg/kg intraperitoneally of dl‐amphetamine‐SO4. Control levels of NA were not reached until 96 hours after a single injection of amphetamine, while the drug disappeared from the brain and plasma within 12 hours. Amphetamine was found to disappear from rat tissues in a poly‐phasic pattern after intraperitoneal administration. The brain/plasma ratio was 9.0 ± 0.3 (mean ± S. D.). Parahydroxynorephedrine was identified in the brain and heart as a metabolite of the d‐isomer of amphetamine. Parahydroxynorephedrine, the apparent T1/2of which was estimated to be about 22 hours, seems to be responsible for the prolonged depletion in the brain and heart NA levels caused by amphetamine. However, there was not an exact stoichiometric relation between the NA deficit and the amount ofp‐hydroxynorephedrine present. After pretreatment with desmethylimipramine, which inhibits the parahydroxylation of amphetamine, the NA in the brain and heart was decreased by amphetamine but already returned to control levels in about 12 hours. It is concluded that the persistent depletion of brain and heart NA induced by amphetamine is caused by the incorporation ofp‐hydroxynorephedrine as a false transmitte

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00580.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Abstract:Thirteen sulfa drugs have been investigated. Their degree of binding to human serum albumin has been studiedin vitroat varying pH. It was found that the degree of binding increased remarkably near the pKa value. A drug with a low pKa has a comparatively high degree of binding at physiological pH whereas a drug with a high pKa has a low degree of binding at this pH. It is shown that a good fit of experiments at a number of pH values is obtained when a modified Scatchard equation is used:This shows that the uncharged species is hardly bound at all. The variation in binding ability among similar ions also depends on the hydrophobic bonds, which are correlated to the partition coefficient of the drug between octanol and water. A quantum mechanical approach has started which shows a correlation between degree of binding and distribution of electronic charge within the drug molecules. Some data are presented.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb03284.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Electrically stimulated isolated rat hearts were perfused with a Ringer solution containing a low concentration of K+. At the end of a control period of 20 min. the cumulative K+loss from the hearts was approximately 30 meq./kg dry weight. This value was used in each experiment as reference (100 per cent) for the total loss found after a subsequent additional test period of 30 min. The addition of promazine and thioridazine to the perfusate at the end of the control period reduced the further K+loss. The values found in the different groups at the end of the test period were: Control group (10 hearts): 154 ± 11.6 per cent; with promazine 10‐5M added (8 hearts): 103 ± 5.6 per cent; with promazine 2.5 × 10‐5M added (10 hearts): 74 ± 10.5 per cent and with thioridazine 10‐5M added (8 hearts): 110 ± 5.8 per cent. In another type of experiments, ouabain 1.5 × 10‐6M was added at the end of the control period. This drug caused an increased K+loss (181 ± 14.2 per cent) and ventricular fibrillation in 6 out of 8 hearts. Promazine 2.5 × 10‐5M added before ouabain, prevented the development of fibrillation in another group of 7 hearts, and also markedly reduced the K+loss. It is concluded that phenothiazines reduce the K+permeability of the heart

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00581.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb03285.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The inhibitor of tyrosine hydroxylase, α‐methyltyrosine methylester (H44/68), was given intraperitoneally to mice. Following this the motor activity was measured at varying intervals of time and as an index of the activity of tyrosine hydroxylase, the net amounts of3H‐noradrenaline and3H‐dopamine formed in the brain from3H‐tyrosine during one hour were assayed. The hydroxylation of tyrosine was markedly inhibited soon after the administration of the inhibitor while the motor activity declined more slowly. Sixteen hours after the administration of the inhibitor, the motor activity and the amine synthesis were normal and restored to 60 per cent of the normal respectively. The results are discussed in relation to previous data obtained in mice on endogenous brain catecholamine levels after a corresponding injection of H44/68. It is suggested that after inhibition of the synthesis, motor activity depends on the store of catecholamines. However, motor activity appears to be maintained at a low amine level provided that the synthesis is not i

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00582.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Whole body autoradiography of mice 2, 20, 60 and 240 min. after intravenous injection of14C‐mestranol showed a rapid and high accumulation of mestranol and/or its metabolites in the adrenal cortex, brown fat and the nervous system. A rather high uptake was also registered in the walls of the follicles and in the corpora lutea. Thin‐layer chromatography of methylene chloride extracts indicated demethylation of14C‐mestranol in the body since labelled substance(s) with the same chromatographic behaviour as ethynyloestradiol was/were found in the liver, brown and body fat and in the combined extract from ovaries and u

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00583.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY