摘要:

Abstract:The effects of the local anaesthetic mepivacaine and its optically active isomers on mechanical activity, as well as the uptake and mobilization of Ca++, on phosphorylase and phosphodiesterase activity and on the content of cyclic AMP have been studied in smooth muscle. In low concentrations L(+)‐mepivacaine had a contracting action on the rat portal vein and the guinea pig taenia coli, whereas D(‐)‐mepivacaine had a predominantly relaxing action. The contracting action was probably associated with a mobilization of tissue bound Ca++. In higher concentrations both isomers had a marked relaxing action, the D(‐)‐isomer being the most potent. The relaxation was competitively counteracted by Ca++, Ba++and Sr++, but not by K+, histamine or noradrenaline. The uptake of45Ca++was reduced; D(‐)‐mepivacaine tended to be more potent than L(+)‐mepivacaine. The content of cyclic AMP was increased by DL‐mepivacaine in taenia coli and by L(+)‐mepivacaine, but not by D(‐)‐mepivacaine in the portal vein. During isometric conditions of taenia coli the increased content of cyclic AMP was partly caused by an adrenergic β‐receptor stimulation and partly by a Ca++‐depending reduction of th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03596.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract:24 male NMRI mice weighing about 17 g each were divided into two equal groups. Group 1 was treated intraperitoneally with methyl mercury nitrate. The dose was 0.3 mg Hg/kg in 0.5 ml water. Group 2, which was kept as a control, was treated with 0.5 ml water intraperitoneally. After 7 days all the mice were sacrificed. As seen by electron microscopy, the smooth endoplasmic reticulum was proliferated and vesicular in all the mice treated with methyl mercury. The mean liver microsomal protein content was significantly increased in group 1 as compared to group 2 (the controls).

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03597.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract:Mice of different ages, from newborn to 26‐day old, were injected intraperitoneally with 1 mg/kg of14C‐nicotine and the nicotine concentrations in the blood and brains were determined 10 minutes after the injection. In 3‐day old and 12‐day old mice the nicotine concentrations in the blood and brains were also determined 1, 2.5, 5, 20 and 60 minutes after the injection. In addition, the nicotine distribution in 3‐day old, 12‐day old and 26‐day old mice was studied by whole‐body autoradiography. The results showed that the ability of the brain to accumulate nicotine increases with age. In addition there were also changes in the distribution of nicotine w

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03598.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract:Time‐dated pregnant (day 21–22) Sprague‐Dawley rats were infused intravenously with morphine 5 mg/kg per hr for periods up to 4 hrs. The blood, brain and placenta of maternal rats and the blood and brain of foetuses were collected and analyzed for morphine content. The morphine concentration in the blood of maternal and foetal rats was maximal after infusions for 3 hrs; at the maximum, the maternal concentration was 2800 ng/ml and the foetal concentration was 1900 ng/ml. The morphine levels of the brain were also maximal at 3 hrs. The foetal level, 2200 ng/g, was not significantly (P>0.05) different from that of foetal blood, whereas the maternal brain level, 600 ng/g, was less than one‐fourth of the maternal blood level. The highest concentration of morphine in the placenta, 6200 ng/g, was also attained after infusion for 3 hrs. These data indicate that the placenta acts as a barrier to the passage of morphine from the maternal animal to the foetus and that a blood brain barrier to morphine exists in the adult but not in the foetal rat. Similar studies showed that an effective blood brain barrier is not present in 20 day old rats. Tolerance to the analgesic effect of morphine, 10 mg/kg subcutaneously, was demonstrated in non‐pregnant adult female rats 2 to 3 days following infusion of morphine, 5 mg/kg per hr for 4 hrs. Reaction times to a nocioceptive stimulus were thus significantly reduced at 1 hr after the test dose (from 19.6 sec. ±2.9 S.E.M. in untreated control animals to 6.8 sec. ±0.4 S.E.M. in the morphine infused animals). The saline infused rats had reaction times after the injection of morphine which did not differ significantly from the untreated control rats. Approximately 20 days after the infusion of morphine to day 21–22 pregnant rats the reaction times to a test dose of morphine were no longer significantly different from those of control rats given the test dose of morphine. The offspring of morphine infused rats were then tested for analgesic response to morphine, 0.45 mg/kg subcutaneously, at approximately 12 days of age and compared with offspring of saline infused rats. The reaction times for offspring of the morphine infused rats 1 hr after the test dose of morphine (26.2 sec. ±1.1 S.E.M.) were significantly greater than those of the offspring of saline infused rats (20.9 sec. ±1.5 S.E.M.). A rapid method for preparing isolated nuclei from adult and foetal rat brain in high yield, using detergent treatment and a onestep centrifugation on a discontinuous sucrose gradient, is described. DNA, RNA and protein content the maternal or the foetal brains, it is still possible that morphine could selectively alter RNA and protein synthesis in the brain without causing a significant change in the overall content of either RNA or protein in ac

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03599.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract:Among the alkyl‐substituted amino ethers derived from diphenhydramine, bufenadrine, 2‐[(o‐tert‐butyl‐α‐phenylbenzyl)oxy]‐N,N‐dimethylethylamine, is a remarkable example of the role of structural factors in liver toxicity. Non‐published toxicological investigations with both optical isomers of this compound revealed that (–)bufenadrine is exclusively or mainly responsible for the toxic activities of the racemic compound. Metabolic studies in rats with both optical isomers labelled N‐14CH3showed that after a single dose profound differences already occur with regard to their metabolic fate. Over the period studied the elimination of radioactivity after a dose of both 2 mg/kg, intravenously, and of 10 mg/kg, orally, of the (–)isomer was lower in the urine, faeces and bile and higher in the respiratory air than with the (+)isomer. When an oral dose of 50 mg/kg was given, the elimination in the respiratory air, too, was lowest in the case of the (–)isomer. Since no significant difference in binding to serum constituents or to homogenated liver tissue was observed, it seems likely that the metabolic differences originate in the liver. The data obtained suggest the inability of the liver to metabolize (–)bufen‐adrine at a rate sufficient to prevent the accumulation of the substance which tr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03600.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract:The effect of phenobarbital pretreatment has been studied on cerium induced impairment of drug metabolism in rat liver. Male rats were divided into four groups: (1) controls, (2) receiving cerium intravenously 2 mg/kg, (3) pretreated with phenobarbital and (4) receiving the same amount of cerium as in group 2 after pretreatment with phenobarbital as in group 3. The pretreatment had a clear protective effect both against the cerium induced impairment of oxidative drug metabolism and the elevation of some enzyme activities. The pretreatment also normalized the decrease in blood glucose and the increase in plasma free fatty acids caused by cerium.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03601.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract:The dose‐mortality curves for dl‐amphetamine after intraperitoneal administration of 10–180 mg/kg of it to adult and developing mice in 7 age groups from 3 to 30 days were determined. The dose‐mortality curve of adult mice was polyphasic. A 100 % mortality was obtained with 100 mg/kg of amphetamine. In developing mice the curves, polyphasic as well, were shifted to the right. At the age of 3 days the mortality caused by 180 mg/kg was only 68 %. With increasing age the animals became more sensitive to the drug, responding partially like the adults from the age of 18 days. The toxicity calculated in relation to the surface area remained unchanged, although the differences between the age groups of developing mice became smaller. In adult mice, pretreatment with 5 mg/kg of amphetamine protected against subsequent toxic doses of the drug, especially in the lower dosage range. Pretreatment given 4 hours before the toxic doses afforded the best protection. It is assumed that the immature CNS of developing mice is partially responsible for the increased tolerance to the drug. The polyphasic shape of the graphs and the protection afforded by the pretreatment reflect the complex lethal actions of amph

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03602.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract:The brain noradrenaline (NA) and dopamine (DA) content of adult and developing mice of 3 age groups (3–5, 13–15 and 32–35 days) was assayed and found to increase with age. In adult mice 4 hrs after the administration of 50 mg/kg of amphetamine the brain NA content was decreased by 65 %. After 100 mg/kg of amphetamine the mice died in 25 min., but the NA and DA levels were only slightly decreased. In all age groups of developing mice, the doses of amphetamine sufficient to be lethal in 30 min. (100–160 mg/kg) caused only a slight decrease or even an increase in brain NA and DA levels. In developing mice surviving 60 min. after amphetamine, the brain amines were massively depleted. In adult mice the brain NA content in 1 hr and 4 hrs after the pretreatment dose of 5 mg/kg of amphetamine decreased by 20 %. The dose of 60 mg/kg 4 hrs after the pretreatment caused a massive depletion in brain NA and DA content 1 hr after the latter injection. Even though the mice survived. The lack of correlation between brain catecholamine depletion and amphetamine toxicity reflects the complex lethal mechanisms induced by t

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03603.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract:The mechanical effects and the alterations in42K‐efflux produced by carbachol, noradrenaline, adrenaline, phenylephrine and isoprenaline have been studied in circular strips from the fundus of rabbit stomachs. Carbachol, noradrenaline, adrenaline and phenylephrine caused sustained contractions of the preparations, and produced a temporary, but statistically significant increase in K‐efflux. A rough correlation was found between the magnitudes of these two effects. Isoprenaline reduced tone in strips which were contracting in response to carbachol, but had no effect on K‐efflux. It is suggested that the increase in tone and K‐efflux produced by noradrenaline, adrenaline, and phenylephrine is due to stimulation of adrenergic α‐receptors. Since the alteration in K‐efflux is only temporary it would appear that K‐efflux is associated with the excitatory processes, but not with those which maintain t

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03604.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract:The properties of 4‐methylpyrazole (4‐MP) as an inhibitor of ethanol metabolism were investigated in rats. No effect was seen on enzymatic determination of ethanol. 4‐MP in doses of 0.0053–3.0 mmol/kg brought about a competitive inhibition of the metabolism of 32.6 mmol ethanol per kg body weight ranging from 20.8 to 80.5 %. A dose of 0.017 mmol 4‐MP per kg gave an inhibition of 50 %. By varying the interval between the administration of 4‐MP and ethanol from 15 min. to 48 hrs, it was found that the inhibitory effect disappeared after 12 hrs. The influence of 4‐MP on ethanol‐induced incoordination was measured by a modified tilting‐plane technique. The mean maximal impairment was significant in all conditions, when compared to the controls. For ethanol alone the mean maximal impairment was 11.9 %, for 4‐MP alone 7.2 % and for ethanol + 4‐MP 14.9 %, the effect lasting for 8 hrs. Thus, 4‐MP exerts significant central depressant effectsper se, and produces an enhancement and a prolongation of ethanol‐induced effects o

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb03605.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY