摘要:

Abstract:DL‐penicillamine and dimercaptopropanol (BAL) increase the biliary excretion of mercury after the injection of methyl mercuric chloride. The effect is sex dependent and dependent on the time interval between mercury injection and the treatment. The time dependent effect is related to the excretion of both inorganic mercury and the intact organo‐mercurial. The results indicate that a combined use of chelating agent and the previously described resin which interrupts the enterohepatic circulation should be valuable for the treatment of exposure to organic or inorganic mercury compou

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01446.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The catecholamine content in the mouse brain has been investigated after administration of analgesic doses of salicylic acid. Doses of 300 and 450 mg/kg salicylic acid given orally did not produce any significant changes in brain noradrenaline or dopamine levels in comparison with untreated or placebo treated animals. After inhibition of the rate limiting step of the catecholamine synthesis, salicylic acid in a dose of 300 mg/kg administered orally produced significant acceleration in the decrease of brain noradrenaline induced by the synthesis inhibitor. This acceleration was significantly greater in mice showing analgesic activity and in these animals a significant acceleration was also found in brain dopamine. Furthermore, after inhibition of dopamine β‐hydroxylase with disulfiram, salicylic acid produced a significant reduction of the brain noradrenaline in animals showing analgesic activity. No corresponding changes were found in dopamine concentrations. The results obtained are similar to those obtained with morphine and it seems possible that salicylates may exert a part of their central analgesic action by interference with noradrenergic or dopamin‐ergic neurons. The investigations also showed that the analgesic test procedure used and the manner of injection did not seem to evoke any stress in the animals sufficient to produce changes in the turnover rate of brain noradrenaline or dopa

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01447.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Nociceptive stimulation has been performed in rats with a technique which should allow us to study different pain projection levels within the central nervous system. Three different types of thresholds were studied by electrical stimulation and the stimulus responses were qualitatively and quantitatively divided into a) motor response b) vocalisation and c) vocalisation after‐discharge. Caffeine and theophylline were able to decrease the thresholds for motor response and vocalisation in a dose‐dependent manner. Both drugs were also able to reduce the thresholds for vocalisation after‐discharge. However, caffeine reduced this response to about 50‐60% of the normal, but not in a dose‐dependent manner, which is contrary to theophylline which, in a dose of 100 mg/kg, decreased the threshold to as little as 20 per cent of the normal. In general, maximum effects were obtained 30 minutes after administration and theophylline produced more long‐lasting effects th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01448.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Polyphloretin phosphate (PPP), a compound with prostaglandin and enzyme inhibitory activities, inhibited the release of histamine from rat mast cells induced by compound 48/80 or bee venom but had no effect on the release of histamine produced by chlorpromazine or n‐decylamine. In perfused cat paws (compound 48/80) and in guinea pig lung tissue (antigen) the histamine release and the formation of slow reacting substance were both inhibited by PPP. The blood pressure lowering effect of compound 48/80 in the cat was antagonized by the intravenous administration of PPP. Experiments with fractionated (dialysed) PPP showed that the high molecular weight fractions of PPP were more potent that the low molecular weight fractions in inhibiting histamine release from rat mast cells. Polyphloroglucinol phosphate, a polymer of the same type as PPP but devoid of any prostaglandin inhibitory (IPG) activity, inhibited the release processes in a manner similar to PPP, indicating that the IPG‐activity of PPP is not associated with its capacity to inhibit release. It is suggested that the inhibition by PPP of the release processes studied may be due, at least partly, to a chemical interaction between inhibitor and releasing ag

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01449.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The fate of atropine in newborn, 3 and 6 weeks‐old, 3 months‐old and adult dogs has been investigated with the tritium‐labelled drug. After subcutaneous injection (0.5 mg/kg) maximal plasma concentrations of radioactivity were obtained after 0.5 hr in the two oldest groups and after 1‐1.5 hrs in the three youngest groups. The plasma half‐life of radioactivity was considerably longer in the newborn animals than in the other groups (11.5 hrs as against 3.5‐5.5 hrs). In the three youngest age groups, the urinary excretion of radioactivity was about half that in the adult animals, who excreted about 40 per cent of the injected radioactivity in 4 hrs. Between 50‐90 per cent of the radioactivity in the urine was recovered as the unchanged drug in all age groups in the 2 to 4 hrs interval. There were no consistent differences in the pattern of metabolites in the urine between the different age groups. The concentration of radioactivity in the liver, kidney, submandibular gland, heart, skeletal muscle and brain was investigated at 0.5, 1, 2, 4 and 8 hrs after injection (0.5, 2 and 8 hrs for adult animals). In general, there were no significant differences in organ distribution between the age groups. The radioactivity in the brain consisted exclusively of the unchanged drug. The rate of penetration into the brain and the maximal brain concentrations of the drug showed no significant changes with age. Within the hemispheres, a fall in the concentration of atropine from the cerebral cortex to the lateral ventricles was found in all age groups. The binding of atropine to plasma proteins was about 18 per cent over a wide range of concentrations. No difference in plasma bindingin vivowas found between the differe

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01450.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The central effects of atropine, methylatropine and oxotremonne have been investigated in dogs at five different ages, i. e. newborn, 3 weeks, 6 weeks, 3 months and adult. The evaluation of the central effects has been made by behavioural and neurological tests, especially designed for the different age groups. In adult dogs 0.5 mg/kg of atropine and 20 mg/kg of methylatropine cause typical behavioural disturbances, i. e. ataxia, non‐responsiveness, non‐retreating behaviour and increased motor activity, while oxotremorine 0.025 mg/kg produces a pronounced tremor. In the newborn dogs no central effects can be detected with atropine, 0.5‐5.0 mg/kg, or methylatropine, 20 mg/kg. Furthermore, tremor can not be elicited with 0.01‐1.0 mg/kg of oxotremorine in this age group. Among the 3 weeks old puppies, the neurologically and behaviourally most mature animals show central effects similar to those in the adult following 0.5 mg/kg of atropine, while more immature dogs show no symptoms even after 5.0 mg/kg. The sensitivity to the tremorogenic affect of oxotremorine is the same in this age group as in the adult dogs. At six weeks and three months of age the effects of the two drugs are the same as in the adult animals. In order to evaluate the development of the central cholinergic system, the activities of choline acetyltransferase and cholinesterases have been determined in whole brain, cerebellum, caudate nucleus and cerebral cortex in the different age groups. An increase is found in relative enzyme activity from birth up to adulthood.The changes in the effects of atropine and oxotremorine are discussed in relation to the development of the two enzymes, and to other biochemical, pharmacological, electrophysiological and behavioural data known for the dog. It is suggested that the change in sensitivity to the two drugs reflects the development of the central cholinergic system, which parallels the general development of th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01451.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:In the presence of oximes phenylthioacetate is deacetylated and acetylated oximes formed. By measuring the velocity of this transacetylation reaction for a number of oximesin vitro, the slopes are found to differ in a way which resembles the variance in the potency of the oximesin vivoas reactivators for cholinesterases inhibited by alkyl organophosphorous compounds. The observations thus support the hypothesis that oximes as acetyl acceptors might have an effect by inhibition of the synthesis of acetylcholine due to deacetylation of acetyl‐coenzyme

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01452.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Evidence has been adduced that in a series of aminoacylanilides the extent to which enzymatic hydrolysis is effected by liver amidases is dependent on the steric positions of substituents. The significance of hydrolysis for the detoxification of aminoacylanilides was examined by repeated administration of the compounds at a slow rate to rabbits. Compounds that were rapidly broken down by amidases displayed a lower cumulative toxicity than those resistent to the enzymes. On the other hand, there was no evident correlation between the enzymatic activity and the acute intravenous or subcutaneous toxicity (LD50 values) following rapid injection of large doses. The toxic potency in this case was directly releated to the blocking action on the isolated nerve. In the case ofo‐toluidine derivatives, there was a close correlation between the rate of hydrolysisin vitroand the formation of methaemoglobin. With 2,6‐xylidine derivatives, no significant formation of methaemoglobin was observed in spite of rapid hydroly

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01453.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The R(+)‐form of N‐n‐butyl‐3‐piperidyl 2′‐chloro‐6′‐methylcarbanilate (HS 37) was a more potent local anaesthetic than the S(‐)‐form in various types of major nerve block, in infiltration anaesthesia and after topical application (guinea‐pigs, rabbits). The potency ratio varied with the method of administration and was between 2 and 3 in most of the tests. A similar difference in blocking activity was obtained in rate and equilibrium blocks of conduction in sheathed and de‐sheathed sciatic nerve (frogs). The effect of the racemate (infiltration, frog nerve) was intermediate to that of the enantiomers. The R(+)‐form was more toxic than the S(‐)‐form, both intravenously (mice, rabbits) and sub‐cutaneously (mice). Nerve blocking and toxic potencies of the enantiomers were positively correlated with ratios of about the same order of magnitude. The findings may indicate some stereo‐selectivity of action of the enantiomers in the excitable membranes rather than differe

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01454.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:SKF 525‐A at concentrations from 10−5M to 2 × 10−4M inhibits the glucuronidation ofp‐aminophenol (PAP),p‐nitrophenol (PNP), and bilirubin by a clonal strain of rat hepatoma cells (MH1C1) grown in culture. At higher concentrations of SKF 525‐A the glucuronidation of PAP and PNP in a homogenate system from the cell cultures and normal rat liver is also inhibited, PAP to the greatest extent. The inhibition of PAP glucuronidation in the homogenate system appears to be of the non‐co

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01455.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY