摘要:

The effect of morphine on the cat choledochoduodenal junction was studied by means of differentin vivoandin vitromethods.In vivo:Morphine (1‐100 μg/kg) induced increased duodenal activity and increased resistance to flow through the sphincter of Oddi when given intravenously. Atropine (5 mg/kg intravenously) counteracted the effect of 1 μg/kg morphine intravenously on the choledochoduodenal tract, but was ineffective in preventing the spasm caused by slightly increased doses of morphine. Effective α‐adrenoceptor blockade with dibenzyline (2 mg/kg) did not affect the action of morphine. Morphine (0.001–0.02 μg/kg) consistently produced increased duodenal activity and increased passage pressure through the sphincter when administered i.a. in the pancreatic duodenal artery.In vitro:The isolated sphincter and the isolated duodenum were insensitive to morphine in concentrations up to 80 μg/ml in the bath fluid.In vivomorphine is active locally in the cat choledochoduodenal tract but inactive when added to the bath fluid of the isolated sphincter of Oddi or duodenum. The results support the view that morphine exerts its spasmogenic effect on the sphincter region by the release of some endogenous contracting agent. This agent does not belong to the cholinergic or adrenergic nervous system but may be released from the vascular compartment b

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00663.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Nine cases of fatal poisoning, where dextropropoxyphene was the sole or contributory cause of death, have been subjected to forensic‐chemical examination. The patients consisted of four youth addicts, two debilitated women who died after taking a combination of drugs, and three cases of suicide. The extraction method, thin‐layer chromatography, and gas chromatography for the determination of dextropropoxyphene have been described. The concentrations of dextropropoxyphene in the gastric contents, blood, liver, brain, bile, small intestine contents, kidneys, urine, and where it was appropriate also in the muscle and injection zone, have been recor

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00664.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Mice, pretreated with reserpine and the inhibitor of monoamine oxidase, nialamide, were administered3H‐noradrenaline followed by protriptyline or amphetamine or both. The3H‐noradrenaline that accumulated in the heart was released by amphetamine but not by protriptyline. Protriptyline was able to prevent the release induced by amphetamine when given before but not after this drug. In a parallel study, nialamide was excluded and3H‐noradrenaline was replaced by3H‐α‐methylnoradrenaline. In this experiment too, protriptyline, in spite of having a releasing action of its own, was able to prevent the amine release brought about by amphetamine. A study of the subcellular distribution providing three fractions: coarse, particulate and supernatant, showed that the release of3H‐α‐methylnoradrenaline brought about by protriptyline and amphetamine was primarily from the coarse and supernatant fractions. Guanethidine, given instead of protriptyline, only partly prevented the amphetamine induced release of3H‐α‐methylnoradrenaline; however, the release from the particulate fraction was completely inhibited. It is concluded that amphetamine has to be transported into the adrenergic neuron via the amine transport mechanism of the cell membrane, the so‐called “amine pump”, in

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00665.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

The capacity of 9 biochemicals to interfere with gas chromatographic exclusion screening analyses for volatile agents encountered in forensic blood samples was studied. The chloroform extractabilities and gas chromatographic retentions on OV‐17 (at 160° column temperature) of 9 biochemicals were examined. On direct chloroform extracts of blood, gas chromatographic peaks were obtained with indole, 2‐phenylethylamine and β‐hydroxybutyric acid. No gas chromatographic peaks were obtained with glycine, cholesterol, cortisol, urea, tyramine and stearic acid. The retention distance of these three biochemicals interfered with the retention distance of the volatile drugs i. e. methyl salicylate, terpin hydrate, phenyl salicylate, amphetamine, acetanilide, and ca

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00666.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

The sensitivity of rats to hexobarbital was measured in two ways: 1. By a threshold dose. Here the amount of hexobarbital needed to obtain a burst suppression of one second or more in the EEG was determined. 2. By ensuing anaesthesia times. The time at which the righting reflex was absent, after a threshold dose had been infused, was determined. Reserpine (2.5 mg/ kg subcutaneously) administered 0‐6 hours before the threshold determination, increased the threshold doses by approximately 20 per cent as compared to a pre‐experimental value. The ensuing periods of anaesthesia were then increased by 50 to 110 min. over the pre‐experimental values of around 20 min. The mono‐amine oxidase inhibitor pargyline (50 mg/kg subcutaneously) given alone one hour before the threshold determination had no effect on the threshold dose or on the ensuing periods of anaesthesia. If DOPA (6–12.5 mg/kg) was given 15 min. after pargyline the threshold doses were reduced by 50 per cent. A significant increase in the ensuing periods of anaesthesia of 40 min. was seen but only in the animals treated with 6 mg/kg DOPA, i.e. not if the higher dose had been used. 5‐hydroxytryptophane (5.0 mg/kg subcutaneously) was also given 15 min. after pargyline. This dose caused a decrease in the threshold by 20 %. The ensuing periods of anaesthesia was shortened by approximately 20 min. All animals died after 5‐hydroxytryptophane and pargyline. This mortality was not caused by the hexobarbital infusion. In normal individuals with widely varying threshold and even in barbiturate tolerant individuals, the ensuing periods of anaesthesia are very similar. This is in contrast to the results obtained in the presen

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00667.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Previous experiments have shown that when14C‐histamine is incubated with human faeces, the radioactivity at times disappears from the fluid fraction. The present study describes a mechanism involved in histamine decay that might explain this phenomenon and that also might be operative in thein vivodetoxication of dietary histamine as well as of histamine formed in the lumen of the gastrointestinal tract. Freshly expelled human faeces were homogenized and incubated in a closed system at 38° in an atmosphere of N2with either ring‐labelled and unlabelled histamine or ring‐labelled and unlabelled N‐acetylhistamine.14CO2was collected on a paper cylinder moistened with NaOH. Considerable formation of14CO2from histamine was found in the faeces of 3 of 6 healthy subjects (15–42% recovered as CO2). These results demonstrate that the imidazole ring of histamine has been ruptured.14CO2formation from N‐acetylhistamine was demonstrated only in faecal samples with an inherent ability to form CO2from histamine. Since N‐acetylhistamine is deacetylated by human faeces, the formation of histamine may be an obligatory step in the ring rupture of N

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00668.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

The disappearance of labelled catecholamines formedin vivofrom14C‐tyrosine in the whole rat brain and in different regions of the rat brain has been studied. The elimination of the labelled amines from the brain followed first order kinetics between one and ten hours after14C‐tyrosine administration. The half‐lives were 2.9 hours for14C‐dopamine and 5.3 hours for14C‐noradrenaline. The rate of disappearance of14C‐dopamine was highest in the cerebral cortex and striatum and lowest in the cerebellum. The rate of disappearance of14C‐noradrenaline was highest in the cerebellum and lowest in the diencephalon. The use of the disappearance of labelled catecholamines as a measure of turnover of endogenous amines is discussed on the basis of results obtained with the tyrosine hydroxylase inhibitor H 44/68 and the dopamine‐β‐hydroxylase inhibitor FLA 63. It is suggested that FLA 63 accelerates noradrenaline turnover and also affects dopamine neurons in the brain. In accordance with previous studies on the accumulation of labelled catecholamines formed from14C‐tyrosine in rat brain regions, chlorpromazine accelerated the disappearance of14C‐dopamine in the striatum but had no significant effect in the other regions. The disappearance of14C‐noradrenaline was not influenced by chlorpromazine in any of the regions studied. The results support the view that chlorpromazine accelerates dopamine turn

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00669.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

The metabolism of 3,4‐benzpyrene (BP) and N‐methylaniline (MA) in several tissues of the immature human foetus and in the human placenta was studiedin vitro.The highest metabolizing activity of both substrates was detected in the liver. Compared to adult rat liver the range of hepatic metabolic activity varied from 5 to 10% for BP hydroxylase and from 5 to even 50% in some foetuses for MA demethylase. Adrenal gland homogenates had measurable BP and MA metabolizing activities. In the gastro‐intestinal tract, brain, kidneys and lungs there was only negligible activity or no activity at all. In one out of five placentas studied, enzyme activity comparable to that in the liver was detected. In foetal liver 12,000 × g supernatants, the Michaelis constants were 2.6 × 10‐5M for BP hydroxylase and 1.2 × 10‐4M for MA demethylase. The cofactor requirements of these enzymes suggested that they are drug metabolizing mixed‐function oxidases. Both enzymes were inhibitedin vitroby other compounds known to be substrates of liver microsomal drug metabolizing enzymes in a concentration range from 0.1 to 20 mM. The level of glucose‐6‐phosphate dehydrogenase activity in the foetal liver was found to be the same or even higher than in the adult

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00670.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

A number of cyclic quaternary ammonium derivatives structurally related to acetylcholine were tested for their inhibitory effect on choline acetyltransferasein vitro.They had no effect. The alcohol derivatives in this series of compounds were not acetylated by the enzyme. The tertiary amine 2‐dimethylaminoethyl chloroacetate and a few related compounds had inhibitory activityin vitro.2‐Dimethylaminoethyl chloroacetate was the most active of these compounds, being about half as potent as the quaternary derivative choline chloroacetate. It inhibited the enzyme uncompetitively with regard to choline as well as acetyl‐CoA, the Kivalues being 1.2 × 10‐4M (choline) and 4 × 10‐5M (acetyl‐CoA) under the conditions used. 2‐Dimethylaminoethyl chloroacetate and two of the other active compounds had no effect in high doses on the acetylcholine level in the mou

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00671.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Newborn rats were given intraperitoneal injections of 20 mg/kg body weight of guanethidine daily for 8 days. About 3 weeks later, they were killed together with their untreated litter mate controls at the age of one month. Guanethidine caused destruction of the superior cervical and coeliac ganglia, the size of which was about 10% of that of the control ganglia. The number of nerve cells in the ganglion remnants was also reduced. The mean number of the small intensely fluorescent (SIF) cells of the superior cervical ganglion increased from 479 cells/ganglion to 1427, and those of the coeliac ganglion from 198 to 1071 cells/ganglion, after guanethidine administration. The number of SIF cells increased in normally existing clusters from which grew out finger‐like cell protrusions. Adult animals injected with 20 mg/kg body weight of guanethidine daily for 14 days and killed on the 15th day had superior cervical ganglia of slightly increased size. The space between the ganglion cell bodies was much increased and was infiltrated by numerous round‐nucleated cells, the cytoplasm of which was non‐fluorescent. The ganglion cells showed degenerative signs of varying degree, such as loss of basophilia and amine fluorescence. No increase in the number of SIF cells was observed. It is concluded that guanethidine causes a chemical sympathectomy accompanied by hyperplasia of the SIF cells in newborn rats, and severe degenerative changes with round cell infiltration in the sympathetic ganglia of adult

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1972.tb00672.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY