摘要:

Saviprazole (HOE 731), a substituted thienoimidazole, caused a dose-dependent inhibition of gastric acid secretion in dogs and rats with ID50 values which were not significantly different from that of omeprazole indicating that both compounds are equally effective. The duration of action in dogs lasted for more than 24 h and was dependent on the state of stimulation. Measurement of serum concentrations of 1 mg/kg saviprazole after intravenous or intraduodenal administration revealed a bioavailability of about 60 % in dogs. The elimination half-life was about 30 min following both routes of administration. In rats basal acid secretion was inhibited by saviprazole. In addition stimulation of acid secretion by histamine, desglugastrin, carbachol and isobutylmethylxanthine-forskolin was equally inhibited. This was in agreement with the known mechanism of action, inhibition of the gastric proton pump which is the last step of acid secretion within the parietal cell. Surprisingly, at high dose levels, saviprazole differed from omeprazole. After saviprazole, 1 mg/kg i.v. to dogs, acid output dropped to zero but recovered within 30 min to a level of 90%, whereas omeprazole depressed acid output completely over the whole observation period (4.5 h). Similar results were obtained in pylorus-ligated rats.

ISSN:0031-7012    

DOI:10.1159/000138859

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The role of the cholinergic nervous system in ethanol-induced gastric mucosal damage has been examined in rats. Oral administration of 50 or 80% ethanol produced haemorrhagic lesions which were reduced by atropine pretreatment (0.65, 2.5, 5 or 10 mg/kg injected i.p.); there was lesser protection against the higher dose of ethanol. Pirenzepine (a specific M1 receptor antagonist) pretreatment (0.1, 0.2, 1 or 2 mg/kg, injected s.c.) produced a similar anti-ulcer effect. Hexamethonium administration (5 or 10 mg/kg, injected s.c.) also protected against ethanol-induced gastric injury to a similar extent; it also increased the amount of adherent mucus on the glandular mucosa. This action may, therefore, account for the protective action of the ganglion blocker. It is concluded that ethanol may stimulate the stomach wall ganglionic nicotinic receptors to activate the postganglionic fibres and subsequently the muscarinic receptors which would then trigger off some of the ulcerogenic mechanisms in the stomach. However, ethanol could also produce gastric damage via the non-cholinergic mechanisms; this action becomes more prominent in gastric injury produced by high doses of ethanol.

ISSN:0031-7012    

DOI:10.1159/000138860

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Galactosamine (GalN) administration produces hepatitis-like liver injury in animals. The hepatotoxicity of GalN is attenuated by several interventions, including activation of the reticuloendothelial system (RES). Fructose-1,6-diphosphate (FDP) administration significantly increases the phagocytic activity of the RES in animals. Thus, investigations were designed to determine whether FDP affords protection against GalN toxicity. Rats were injected with GalN (375 mg/kg) and treated with 0.9% NaCl (n = 8) or FDP (n = 9). Eight rats were sham-operated. Serum glutamic oxaloacetic transaminase was 40 times higher in the saline group as compared to the FDP-treated rats (p < 0.0001). Glutamic pyruvic transaminase, γ-glutamyltranspeptidase and bilirubin were similarly elevated (saline vs. FDP, p < 0.005, p < 0.01 and p < 0.05, respectively). These values were not different between FDP-treated and sham-operated rats. Extensive hepatic necrosis was observed in all saline-treated rats, whereas in the FDP group only isolated foci of hepatocellular necrosis were noted. The hepatoprotective effect of FDP in this model is attributed to its ability to enhance the phagocytic activity of RES and to suppress release of oxyradicals by the leukocytes during the inflammatory phase

ISSN:0031-7012    

DOI:10.1159/000138861

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In two randomized, placebo-controlled, double-blind studies, the efficacy, duration of action and tolerability of a single morning dose of 25, 50, and 100 mg miglitol (BAY m 1099), an absorbable inhibitor of intestinal α-glucosidases, were assessed after repetitive sucrose or maize-starch loads (50 g of carbohydrates in 400 ml of water each at 08.00, 12.00, and 17.00 h). With sucrose, miglitol reduced the postprandial rise in blood glucose, serum insulin and serum gastric inhibitory polypeptide concentrations at any dosage. This effect was dose-dependent and confined to the first carbohydrate load in the morning, thus indicating the duration of α-glucosidase inhibition of less than 4 h. Sucrose malabsorption, indicated by breath hydrogen responses, occurred dose-dependently with 50 and 100 mg, but not with 25 mg of miglitol. Similarly, symptoms of carbohydrate malabsorption were absent with 25 mg of the inhibitor and mild to moderate after 50 and 100 mg of miglitol. With starch as the substrate, BAY m 1099 led to a significant amelioration of glycemic and hormonal rises after the first meal, but not thereafter. A numerical dose dependency was recognized, but this was not significant at the 5 % level. Symptoms of carbohydrate malabsorption were absent with 25 mg and negligible with 50 mg BAY m 1099, but occurred almost regularly with the 100-mg dose. Breath hydrogen concentrations increased gradually with the dose of miglitol administered. A single morning dose of 25–100 mg of miglitol thus may be useful for the control of postprandial hyperglycemia after breakfast. Due to the duration of action of less than 4 h, this substance should be given with the three main me

ISSN:0031-7012    

DOI:10.1159/000138862

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

l-Tetrahydroberberine-d-camphor sulfonate (THB-CS) possessed an inhibitory effect on apomorphine-induced chewing movement in a similar manner to that of tetrahydroberberine (THB). Both compounds enhanced barbiturate-induced hypnosis. They did not have an anticonvulsant effect on convulsive seizures induced by bicuculline, pentetrazole or strychnine. THB and THB-CS blocked dopamine-stimulated adenylate cyclase activity. These compounds showed almost equipotent affinities to dopamine D1 (3H-SCH-23390) and D2 (3H-spiperone) receptors but did not have significant affinity to μ-opioid, muscarinic and α2-adrenergic receptors, and benzodiazepine binding sites. Furthermore, both compounds did not elicit cataleptogenic behavior, even at very high doses. These data suggest that THB and THB-CS have a central depressant effect through both D1 and D2 dopaminergic receptors and may have different modes of action from that of standard neuroleptic

ISSN:0031-7012    

DOI:10.1159/000138863

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Previous studies have demonstrated that the ability of the in vitro whole bladder to empty in response to bethanechol administration was inhibited by anoxia while its ability to generate pressure decreased only slightly. One question was not addressed by these early studies: Is the anoxic effect selective for receptor-mediated contractile stimulation (as opposed to non-receptor-mediated contractile stimulation)? The present study was designed to compare the effect of anoxia on the ability of the in vitro bladder to generate pressure, sustain pressure, and empty in response to field stimulation (FS), bethanechol and KCl administration.

ISSN:0031-7012    

DOI:10.1159/000138864

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138865

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138866

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138858

出版商:S. Karger AG    

年代:1991

数据来源: Karger