摘要:

In experiments on mice it has been shown that 2‐amino‐4‐phenylsulphonylbenzenesulphonamide (NSD 3004) has a protective effect against maximal electroshock seizures comparable to the effect of phenobarbital and diphenylhydantoin. This effect was correlated to blood and plasma concentration. NSD 3004 had no central depressant effect but in high doses it exibited a weak diuretic action. Usingin vitroandin vivotechniques the substance was found to inhibit carbonic anhydrase. The carbonic anhydrase inhibitors acetazolamide and sulthiame had a weaker anticonvulsant and a stronger diuretic effect as compared to NSD

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00629.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The biological half‐life in the blood of a new anticonvulsive drug, NSD 3004, was studied in various species. The half‐life in man was about 120 days and from 2–30 days in 3 other mammalian species. The substance is a carbonic anhydrase inhibitor and is bound strongly to the carbonic anhydrase in human red blood cells with a dissociation constant of about 10‐8M. The receptor (drug) concentration is about 100–133 μM in red blood cells which corresponds to the concentration of carbonic anhydrase. The data presented indicate that NSD 3004 is bound to human carbonic anhydrases B and C (HCAB and HCAC) and that the strongest binding is to the C fraction. More than 90% of the NSD 3004 in the plasma is protein bound. This, and the high affinity to the red blood cells, explains the extremely long half‐life of the substance in

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00630.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The effect of some sympathomimetic amines on the rate of disappearance of22Na injected into the hind legs of rats was studied. The technique used was developed particularly for studying the influence of new drugs on capillary blood flow, i.e. the factor primarily determining drug absorption. Decreased capillary circulation (sodium clearance) in the muscle pocket of the sciatic nerve was produced, in order of efficacy, by adrenaline, noradrenaline, levonordefrin, phenylephrine and metaraminol, in concentrations of 10 and 100 μg/ml. Isoprenaline in low concentration (0.01 μg/ml) was found to enhance capillary circulatio

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00631.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Chloromethane was shown to react with human plasma and erythrocytes. Using14C‐CH3Cl, it was found that in plasma radioactivity was bound only by albumin. On hydrolysis the major reaction product was S‐methylcysteine; small amounts of 1‐ and 3‐methylhistidine were found. In plasma, the bound radioactivity corresponds to only 2–3% of the uptake measured using unlabelled CH3Cl, suggesting that other, unidentified volatile products are formed. In erythrocytes, approximately 40% of the uptake was bound by GSH forming S‐methylglutathione. The reaction appeared to be enzyme‐catalysed. Loss of thiol groups of plasma protein and erythrocytes and inhibition of oxygen uptake of erythrocytes could not be demonstrated. S‐Methylglutathione was neither lost from erythrocytes during separation and washing, nor was it hydrolysed. It is postulated that some of the cases of anaemia reported following exposure to chloromethane may be due to lack of

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00632.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Chloromethane reacted with rat and guinea pig brain, liver and kidney. Using14C‐CH3Cl with rat tissue homogenates, the bound radioactivity corresponded with the uptake in the liver and kidney but was lower in the brain.14C‐S‐methylglutathione (GSMe) and14C‐S‐methylcysteine (S‐MeCys) were formed by liver, which did not hydrolyse14C‐GSMe, so that the14C‐S‐MeCys must have been formed directly. Both reactions appear to be enzyme‐catalysed. In the kidney and brain,14C‐S‐MeCys and14C‐GSMe were formed and methylation of cysteine SH‐groups in the mixed insoluble proteins was demonstrated. Traces of radioactivity were found in methionine in the kidney proteins. The kidney and brain homogenates hydrolysed14C‐GSMe. Rapid losses of radioactivity during processing in some kidney experiments suggest that volatile products are formed, but this is not due to fission of S‐methyl groups of S‐MeCys or GSMe. The level of binding was lower in heated tissues, especially in the water‐soluble fraction. Inhibition of respiration of rat brain and inhibition of two thiol‐dependent enzymes could not be demonstrated. It is suggested that loss of GSH and intracellular accumulation of GSMe may account for some of

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00633.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The biliary excretion of some isotopically labelled quaternary ammonium compounds and tertiary amines have been studied in rats after intravenous administration. The elimination of radioactivity into the bile was followed 4–6 hours. The amount of radioactivity eliminated ranged from 0.0–54% of the given doses of activity. Chromatographic studies indicated that only a small fraction of the activity eliminated into the bile was attributable to the original compound in most of the cases in which extensive excretion of radioactivity was noted. Metabolites were formed which seemed to be more polar than the original compounds. Molecular properties for biliary excretion are discus

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00634.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Chloroacetic‐1‐14C acid was given intraperitoneally and the elimination of radioactivity was followed for 3 days. 82–88 per cent was found in the urine and about 8 per cent in the expired air. The faeces (contaminated with urine) contained 0.2–3 per cent and 2–3 per cent remained in the animal. Examination of the urine by paper chromatography showed 2 major metabolites, S‐carboxymethyl‐L‐cysteine and thiodiacetic acid, and small amounts of glycolic acid. The amounts were estimated by isotope dilution analysis giving the following results (percentage of urinary activity): Chloroacetic acid 6–22, S‐carboxymethyl‐L‐cysteine 33–43 (free) and 1–6 (conjugated), thiodiacetic acid 33–42, glycolic acid 3–5 and oxalic acid 0.1–0.2. Carboxymethylcysteine was found to be the precursor of thiodiacetic acid but not of carbon dioxide. When glycolate‐1‐14C was given intraperitoneally, 60–70 per cent of the radioactivity was eliminated as carbon dioxide. Two metabolic pathways are suggested for chloroacetic acid: (1) A major one with an initial formation of S‐carboxymethyl glutathione which is converted to S‐carboxymethylcysteine, part of which is further metabolized to thiodiacetic acid, and (2) a minor one involving a probably enzymatic hydrolysis of the carbon‐chlorine bond with the formation of glycolic ac

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00635.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The accumulation of decamethonium by mouse kidney slices was investigated with particular reference to the possibility that this agent uses a choline transport system. Slices of mice kidneys were incubated (1 hour) in Krebs‐Ringer bicarbonate medium (37°, pH 7.4) containing14C‐decamethonium (2 × 10‐6M) with or without the addition of other drugs. Choline and neostigmine stimulated decamethonium uptake at relatively low concentrations (10‐3M and 3 × 10‐3M choline, 5 × 10‐5M and 10‐4M neostigmine), whereas both agents at higher concentrations (3 × 10‐2M choline, 10‐3M and 10‐2M neostigmine) depressed the uptake. Hemicholinium‐3 (10‐3M), atropine (2 × 10‐5M) and physostigmine (2 × 10‐4M) inhibited decamethonium uptake, indicating that these agents in addition to choline and neostigmine share a common transport mechanism with decamethonium. The initial decamethonium influx (3 minutes incubation) could be stimulated by pre‐incubating the slices (1 hour) with 10‐3M choline or 3 × 10‐4M neostigmine (in the absence of decamethonium) before transfer to a final medium containing only decamethonium. Stimulation can thus be interpreted as an example of accelerative exchange diffusion, which should mean that efflux of choline or neostigmine accumulated by the slices accelerates decamethonium influx. It is concluded that decamethonium uses a specialized transport system, which seems to involve a choline carrier and to be in part at least identical with the system responsible for orga

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00636.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

An investigation was performed to determine whether decamethonium and carbamoylcholine share a common transport mechanism with tetraethyl‐ammonium and N1‐methylnicotinamide in mouse kidney slices. Slices were incubated (1 hour) in Krebs‐Ringer bicarbonate medium (37°, pH 7.4) containing 2 × 10‐6M14C‐labelled decamethonium or carbamoylcholine both in the absence and presence of the drugs. Tetraethylammonium and N1‐methylnicotinamide stimulated decamethonium uptake at relatively low concentrations (5 × 10‐5M and 10‐4M tetraethylammonium, 10‐4M and 5 × 10‐4M N1‐methylnicotinamide), whereas both agents at higher concentrations (10‐3M and 10‐2M tetraethylammonium, 2 × 10‐2M N1‐methylnicotinamide) depressed the uptake. Tetraethylammonium (10‐4M, 10‐3M) and N1‐methylnicotinamide (10‐3M) also inhibited the uptake of carbamoylcholine. The initial decamethonium influx (3 minutes incubation) could be stimulated by pre‐incubating slices (1 hour) with 3 × 10‐4M tetraethylammonium or 5 × 10‐4M N1‐methylnicotinamide (in the absence of decamethonium) before being transferred to a final medium containing only decamethonium. Stimulation can thus be interpreted as an example of accelerative exchange diffusion, which should indicate that efflux of tetraethylammonium or N1‐methylnicotinamide accumulated by the slices accelerates the influx of decamethonium. It is concluded that decamethonium and carbamoylcholine use a carrier mechanism which is also involved in tetraethylammonium and N1‐methylnicotinamide transport. This transport mechanism is most likely in part at least, identical with that responsible for the secretion of tetraethylammonium and N1‐methylnic

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00637.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

In quantitative studies of gastric functions, calculations based on the recovery of an ideal non‐absorbable reference substance from the stomach allow corrections for the loss of the gastric contents through the pylorus. When the gastric contents of histamine stimulated rats were aspirated 45 minutes after oral administration of test meals at pH 6.5 containing phenol red or51Cr‐EDTA, the mean recovery of phenol red (37.0 % ± 1.4) was significantly lower than the corresponding value for51Cr‐EDTA (48.7% ± 2.2). Consequently, when the calculations were based on phenol red as a reference substance, significantly larger volumes of fluid and higher amounts of HCl were estimated to have passed through the pylorus. In a paired comparison with the two compounds given in the same test meal, similar results were obtained. Mucosal binding and absorption of phenol red are suggested as the most likely explanations for the discrepancy. In addition to high stability, inertness, and a more complete recovery, the water‐soluble51Cr‐EDTA complex offers analytical advantages. In the present method51Cr‐EDTA thus seems to meet the requirements of a satisfactory reference substance better th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00638.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY