摘要:

Abstract:The distribution and metabolism of14C‐tamoxifen (a non‐steroidal triaryl ethylene anti‐oestrogen) have been investigated in ovarieectomized mice. The autoradiograms showed accumulation of radioactivity in the liver and the bile as an indication of an excretory pathway, but a rapid and high accumulation was also seen in the lung and the adrenals, organs normally not considered as target organs for tamoxifen. The liver and sebaceous glands could be detected on the autoradiograms up to fourteen days after a single intravenous dose. However, in most organs the amount of retained radioactivity was very low after 24 hours. By using the autoradiograms as a guideline a metabolic study was performed. High concentrations of unmetabolized tamoxifen was detected in the lung and the adrenals as well as in the pancreas. Relatively high amounts of a compound tentatively identified as 4‐hydroxy‐tamoxifen were present in the pancreas and the liver and there were also indications for the presence of N‐desmethyl‐tamoxifen in these tissues. These metabolites are considered to possess anti‐oestr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00958.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Electrocardiographic and haemodynamic changes have been studied in conscious dogs after a sublethal oral dose (20 mg·kg−1) of citalopram. Furthermore, the effects of continuous intravenous infusion of citalopram (10 mg·kg−1per hour) have been studied in conscious and anaesthetized dogs. The findings have been related to plasma levels of citalopram. Severe convulsive attacks occurred in conscious dogs after infusion of 21.3 or 26.5 mg·kg−1and after the oral dose. The convulsions were successfully treated with diazepam. In contrast convulsions were not seen in the anaesthetized dogs. They died from respiratory arrest after infusion of 42.2 or 61.3 mg·kg−1. Atrioventricular and intraventricular conduction was unchanged and electrocardiographic changes were negligible. Sinus tachycardia which could be reversed by diazepam and moderate haemodynamic changes were seen. Since no electrocardiographic changes were seen in conscious dogs even during pauses in the convulsive seizure it is concluded that citalopram does not exert cardiotoxic effects in the dog. Good correlation was found between general clinical findings and citalopram levels in plasma. Conscious dogs were exposed to drug levels exceeding those of the average patient by a factor of about 20, while anaesthetized dogs had considerably higher con

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00959.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:In isolated detrusor from guinea‐pigs and rats substance P (SP) induced concentration‐dependent phasic contractions. Rabbit detrusor strips responded to SP with an initial phasic and an ensuing tonic contraction. The concentration‐response curve to SP in this preparation had a biphasic appearance. Eledoisin (E) caused contractile responses similar to those of SP when tested on the guinea‐pig detrusor. Somatostatin was tested on the rabbit urinary bladder; it caused a concentration‐dependent rise in basal tone, but no phasic contraction. The responses to SP and E were not affected by tetrodotoxin or physostigmine. They were only partly inhibited by high concentrations of atropine and the anticholinergic drug PR 197. Noradrenaline and isoprenaline caused a concentration‐dependent inhibition of the peptide induced responses in guinea‐pig bladder; at high concentrations of the amines this inhibition was almost complete. Indomethacin did not affect the SP induced contractions in the guinea‐pig bladder, reduced the responses in the rabbit detrusor, but increased them in the rat bladder. Contractions elicited by SP and E were rapidly diminished or abolished after 30 min. treatment in a calcium‐free medium. The responses were also inhibited by the calcium antagonist nifedipine. In guinea‐pig preparations depolarized by potassium (127 mM) both SP and E caused a contractile response approximately 20% of that obtained in normal Tyrode solution. It is concluded that SP and E cause contraction of detrusor by a direct effect on the smooth muscle cells, and that this response is dependent on the extracellular calcium concentration. Prostaglandins may be involved in the SP‐induced response o

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00960.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Orphenadrine or imipramine were given intravenously as an infusion to spontaneously breathing, anaesthetized rats until respiratory arrest, the primary cause of death for both drugs. Intravenous injections of physostigmine did not prolong survival. Artificial ventilation prolonged survival for orphenadrine and imipramine by about a factor 3 and the rats died from cardiogenic shock. The cardiotoxic properties of orphenadrine and imipramine express themselves as a progressing disturbance in stimulus formation and conduction, a decrease in dP/dt max and increase in left ventricular end‐diastolic pressure and a decrease in cardiac output caused by the progressing decrease of heart rate. An intravenous injection of physostigmine did not prolong survival and had no favourable effect on the cardiotoxicity caused by orphenadrine and imipramine. Although physostigmine may be useful in the treatment of the anticholinergic syndrome it has, at least in the rat, no favourable effect on the respiratory insufficiency, due to overdoses of orphenadrine and imipramine. Moreover it is not effective in antagonizing the cardiotoxic effects of orphenadrine or imipramin

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00961.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Thioctic acid markedly increases the sulfhydryl and sulphide content of bile. This probably reflects the reduction of thioctic acid in the liver, followed by biliary excretion of a reduced derivative. The total biliary excretion of methyl mercury was not increased. Thionalide markedly inhibits biliary excretion of methyl mercury. Simultaneously, the sulfhydryl and sulphide content of bile decreases. This is probably caused by the conjugation of thionalide to glutathione in the liver, thereby blocking the biliary excretion of methyl mercury. Hexadecylmercaptoacetate increases the biliary content of methyl mercury moderately after a temporary decrease, whereas biliary sulfhydryl and sulphide concentrations were unchanged. Octadecylmercaptoacetate does not change the biliary content of methyl mercury, sulfhydryl and sulphides significantly. Smaller parts of hexadecylmercaptoacetate, octadecylmercaptoacetate and thionalide seemed to be excreted as such in bile. These results indicate that methyl mercury cannot be transported from liver to bile as complexed to the sulphides thioctic acid, thionalide, hexa‐ and octadecylmercaptoacetat

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00962.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:A radioreceptor assay (RRA) for determining benzodiazepines (BZ) has been developed and applied to toxicological analysis of serum samples from 21 patients with acute BZ overdosage. The method was sensitive (e.g., lorazepam 17 nM, diazepam 41 nM), and specific for pharmacologically active BZ derivatives. The reproducibility of the results was good (intra‐assay variation<8%, inter‐assay variation<10%). Concentrations measured by the RRA showed a good correlation with those obtained by gas‐liquid chromatographic analysis of the same samples. The quantitative results represent the sum of one or several parent substances and all biologically active metabolites, in proportion to their receptor binding affin

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00963.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Zinc ions can totally block stereospecific binding of3H‐met‐enkephalinamide (2‐D‐ala‐5‐L‐methionine) to opiate receptor sites in synaptic membranes of the hippocampus, the cerebral cortex and the basal ganglia of the rat brain. Analysis of binding isotherms indicates that this inhibitory effect involves a decrease in both receptor affinity and the number of binding sites. Our data also suggest that the zinc ions react with essential SH‐groups of the opiate receptor. The endogenous concentrations of zinc ions in the hippocampus, the cerebral cortex and the basal ganglia are compatible with the concentrations needed to inhibit opiate receptor bindingin vitro.Especially the hippocampus contains a high concentration of zinc ions, which are localized exclusively in the giant boutons of the mossy fibers. Further, the hippocampal distribution of enkephalin and zinc ions is identical and confined to the mossy fiber zone. Hence, zinc ions may represent important modulators of opiate receptor binding in the central nervous system, particularly in the hippocampal m

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00964.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Rats were fed an all liquid diet for 7–8 weeks. One group received 35% of the calories as ethanol while the other group was pair‐fed carbohydrates. Peritoneal macrophages prepared from ethanol treated rats had lower phagocytosis via the Fc‐receptor and reduced viability in the presence of endotoxin, but their lysosomal enzyme activities measured (β‐glucuronidase, cathepsin D, acid phosphatase and acid DNase) were not different from

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00965.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Absorption and urinary excretion of 2‐14C‐L‐α‐methyldopa (αMD) were investigated in 5 healthy human volunteers. The drug was administered alone, with a mixture of amino acids and with a meal consisting of roast beef. The radioactivity in plasma and urine was not decreased significantly by either treatment, and it was concluded that the overall absorption of the drug was virtually unchanged. The amount of unconjugated αMD in plasma and urine, however, was significantly decreased following administration of the drug with roast beef. As the acid labile conjugates of αMD were practically unchanged an increased biotransformation to other metabolites owing to the protein rich meal was suggested more probable than competition between αMD and amino acids in the specific trans

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00966.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Mice and guinea pigs were intoxicated by three different organophosphates: DFP, paraoxon, and OMPA. After onset of intoxication the animals were treated by either a mixture of atropine plus obidoxim or dexetimide plus obidoxim. The combination of dexetimide plus reactivator proved to be superior to the combination of atropine plus reactivator in case of DFP intoxication. In guinea pig the LD50 of DFP could be increased from about 20 to 1300 μm/kg b.wt. by dexetimide plus obidoxim when applied after the onset of intoxication. Concerning the paraoxon intoxication both antidote mixtures were found to be equally potent, whereas the purely peripheral intoxication induced by OMPA could only be influenced to a minor degree. The tissue distribution of atropine and dexetimide differs markedly, dexetimide being accumulated faster and to a higher degree. Thus the higher penetration rate of dexetimide into the central nervous system is considered to be the reason of its superiority in the treatment of an organophosphate intoxication of rapid onset

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb00967.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY