摘要:

The disposition of quinolinium dibromide (QdB), a highly active agent against murine L1210 leukemia was studied using 14C-labeled drug. Excretion of radioactivity was slow, with only 10 and 16% of the dose eliminated in the urine and 19 and 24% in the feces, 96 h after intraperitoneal administration of QdB to mice and rats, respectively. Plasma levels of 14C were low and decreased with time, whereas tissue concentrations were high and remained elevated. Differences in tissue concentrations observed in the rat 96 h following intravenous and intraperitoneal dosing could be explained by QdB binding. A strong association between QdB and DNA was indicated by the effect of DNA on the absorption spectrum and Sephadex G-200 elution profile of QdB.

ISSN:0031-7012    

DOI:10.1159/000136836

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

The cis-isomer of chlorprothixene (CPX) inhibited the excretory function of the isolated perfused rat liver. It decreased the biliary clearance and transport maximum of sulfobromophthalein (BSP). Calculation of the BSP ‘clearance constants’ suggested that the primary effect of the drug was on excretion and not uptake. The ability of the drug to inhibit the excretion of indocyanine green suggested that the effects of CPX were not the result of inhibition of hepatic conjugative enzymes. Measurement of 14C-erythritol clearance indicated that the deleterious effects of CPX on bile formation were at the canalicular level and that they were mainly on the bile acid-independent fraction of bile. The data indicated that the adverse effects of CPX were at the excretory level of the hepatoc

ISSN:0031-7012    

DOI:10.1159/000136837

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

THC was neither ulcerogenic in ‘semi-fasted’ or 18-hour fasted rats following an oral dose of 100.0 mg/kg nor did it promote fecal blood loss (51Cr-labelled erythrocyte test) in the fasted rat after a dose of 200.0 mg/kg. On the contrary, 200.0 mg/kg of acetylsalicylic acid was ulcerogenic and caused fecal blood loss in the fasted rat. Neither substance caused mortalities at the doses tes

ISSN:0031-7012    

DOI:10.1159/000136838

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

The in vitro addition of (–)-Δ9-tetrahydrocannabinol (Δ9-THC) resulted in a dose-responsive inhibition of the high-affinity specific synaptosomal uptake of both 3H-tryptophan and 3H-choline in mouse forebrain crude synaptosomal preparations. The approximate concentrations of Δ9-THC required to cause a 50% inhibition of the uptake of 3H-tryptophan and 3H-choline were 33 and 16 μM, respectively. Kinetic analysis showed that inhibition of both compounds were consistent with a noncompetitive mechanism. The pretreatment of mice with doses of 10, 30 or 100 mg/kg Δ9-THC had no effect on the subsequent in vitro synaptosomal uptake of either 3H-tryptophan or 3H-choline into forebrain synapt

ISSN:0031-7012    

DOI:10.1159/000136839

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

The technique of morphine pellet implantation was utilized to produce physical dependence on morphine in both male and female rats. At the peak of dependence (96 h), naloxone hydrochloride (1.0 mg/kg s.c.) was administered to precipitate withdrawal and the mean number of ‘wet dog’ shakes was determined for 30 min. A predictable and rhythmic cycle of approximately 6 weeks was observed in the number of ‘wet dog’ shakes in morphine-withdrawn animals. This rhythm was not a sex-related phenomenon; there was no discernable rhythm in total body weight loss during the withdrawal period. The intensity of the withdrawal response was inversely related to the brain concentration of morphine. However, the periodicity of the long-term rhythm in ‘wet dog’ shakes was not similar to that of brain concentrations of morphine. An 8 month study of the in vitro hepatic clearance of morphine in the nondependent rat indicated that there are long-term fluctuations in the rate at which morphine is cleared from the rat liver. Also, development of dependence on morphine in the rat was not found to consistently alter the hepatic clearance of the drug. These findings suggest more than one controlling mechanism in the fluctuation of ‘wet dog’ shakes and that the time of the year at which the study is conducted is an important variable in the determination of the effects of morphine depend

ISSN:0031-7012    

DOI:10.1159/000136840

出版商:S. Karger AG    

年代:1978

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000137061

出版商:S. Karger AG    

年代:1967

数据来源: Karger

摘要:

6 male rhesus monkeys (Macaca mulatta) were treated with 14CH3-N-antipyrine (15mg/kg, i.v.). Antipyrine plasma half-lives (APH) were determined using HSLC, radiometric, and spectrophotometric methods. APHs obtained by HSLC analysis of plasma extracts were lower than radiometric and spectrophotometric determinations. The three procedures were investigated to determine if coextraction of metabolites might be responsible for differences in APH. All three solvent systems extract significant quantities of antipyrine metabolites. N-desmethylantipyrine and 3-hydroxymethylantipyrine may interfere with spectrophotometric determination of antipyrine. While all three methods are capable of detecting changes in hepatic oxidative metabolism, HSLC permits direct measurement of antipyrine concentrations and APH.

ISSN:0031-7012    

DOI:10.1159/000136841

出版商:S. Karger AG    

年代:1978

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000137062

出版商:S. Karger AG    

年代:1967

数据来源: Karger

摘要:

The effectiveness of benzodiazepines arid anticholinergics administered alone or in combination in preventing restraint-immersion and forced exertion-induced gastric mucosal erosion was investigated in mice. The benzodiazepines used were diazepam and chlordiazepoxide HCI and the anticholinergics were propantheline bromide and clidinium bromide. The administration of a benzodiazepine with an anticholinergic resulted in additive or supra-additive protective effects in both systems. In the restraint-immersion system, diazepam combined with propantheline bromide at a ratio of 1 to 13.7 yielded a 4.53-fold supra-additive effect. At ratios of 4.6 or 1.5 parts of propantheline bromide to 1 part of diazepam an additive effect was observed. One part of diazepam, when combined with 1.4 to 12.0 parts of clidinium bromide resulted in supra-additive effects of about 1.5-fold. The co-administration of chlordiazepoxide HCI and clidinium bromide in ratios of 2 to 1 or 2.5 to 1 resulted in supra-additive effects of 2.4- and 1.85-fold, respectively. At higher and lower ratios additive effects were demonstrated. In the forced exertion system, diazepam combined with either anticholinergic resulted in supra-additive effects of 2- to 3-fold which occurred at ratios of diazepam to the anticholinergic varying over an 8-fold range. The co-administration of 2 parts of chlordiazepoxide HCI and 1 part of clidinium bromide resulted in a 2.84-fold supra-additive effect in the forced exertion system. These results are discussed in relation to the use of benzodiazepine anticholinergic combinations in the treatment of human gastric and duodenal ulcer disease.

ISSN:0031-7012    

DOI:10.1159/000136842

出版商:S. Karger AG    

年代:1978

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000137063

出版商:S. Karger AG    

年代:1967

数据来源: Karger