piperidines and Peptic-Ulcer

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bicarbonates; Carnosine; Chalcone; Chalcones; Diterpenes; Enprostil; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Mucus; Organometallic Compounds; Peptic Ulcer; Piperidines; Prostaglandins; Sucralfate

Potent antisecretory agents, such as histamine H2-receptor antagonists and proton pump inhibitors, have achieved great improvement in peptic ulcer therapy. It has, however, been reported that incidence of ulcer relapse is high after discontinuation of these drugs. Insufficient efficacy against NSAID-induced ulcers is also critical. Lafutidine is a novel histamine H2 antagonist with gastroprotective activity. Lafutidine exhibited potent and long-lasting H2 antagonism and prolonged antisecretion. In addition, lafutidine showed a gastroprotective effect against noxious agents-induced gastric mucosal damage through capsaicin-sensitive afferent nerves. Lafutidine showed antiulcer activities against acute ulcer models, prevented gastric ulcer relapse of acetic ulcer, and accelerated the healing of indomethacin-induced antral ulcers in rats. These results suggest the advantage of the combined antisecretory and gastroprotective activities. In clinical studies, lafutidine showed prolonged antisecretion, healing effect against gastric and duodenal ulcers and gastritis, and its potency was equal or superior to that of conventional H2 antagonists. Additionally, lafutidine induced a high transition rate to the E0 stage determined by endoscopical ultrasonography, suggesting the high quality of ulcer healing. Furthermore, effectiveness of lafutidine against NSAIDs-induced ulcer was high. From these results, lafutidine is equal or superior to conventional H2 antagonists in antiulcer potency, and it may be useful for the prevention of ulcer relapse and or treatment of NSAIDs-induced gastroduodenal damage.

Topics: Acetamides; Animals; Anti-Ulcer Agents; Gastric Acid; Gastric Mucosa; Histamine H2 Antagonists; Humans; Peptic Ulcer; Piperidines; Pyridines; Rats

Dyspepsia affects one in four Australians; of those who present in general practice, the majority will have functional or non-ulcer dyspepsia, with no structural explanation for their symptoms. Older patients who present for the first time with dyspepsia, and those with 'alarm features' deserve immediate investigation (preferably by upper endoscopy), to exclude cancer, peptic ulcer or oesophagitis. Other patients may be given empiric therapy (for example, a prokinetic or H2 blocker) initially, but require investigation if this fails. The role of Helicobacter pylori infection in functional dyspepsia is uncertain.

Topics: Adult; Aged; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Child; Cholelithiasis; Chronic Disease; Cisapride; Diagnosis, Differential; Domperidone; Dopamine Antagonists; Dyspepsia; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metoclopramide; Peptic Ulcer; Piperidines; Stomach Neoplasms

Roxatidine acetate is a histamine H2-receptor antagonist which, after almost complete oral absorption (greater than 95%), is rapidly converted to its active metabolite, roxatidine, by esterases in the small intestine, plasma and liver. Roxatidine is a potent inhibitor of basal and stimulated gastric acid secretion in animals and humans and, like most other H2-receptor antagonists, has no anti-androgenic effects and does not interfere with the hepatic metabolism of other drugs. Large-scale trials have shown that roxatidine acetate 150mg per day is as effective as standard doses of cimetidine and ranitidine in the treatment of patients with duodenal or gastric ulcer, and that roxatidine acetate 75mg in the evening is likely to become a 'standard' regimen for the prevention of peptic ulcer recurrence. Preliminary data also suggest that roxatidine acetate may be useful in the treatment of reflux oesophagitis and stomal ulcer, and in the prevention of pulmonary acid aspiration. Roxatidine acetate is an H2-receptor antagonist which has been well tolerated in clinical trials. However, broader experience is required before definitive statements about tolerability relative to other H2-receptor antagonists can be made, and before the role of roxatidine acetate in the treatment of reflux oesophagitis and stomal ulcer, and the prophylaxis of acid aspiration pneumonitis, can be clearly defined.

Topics: Animals; Drug Evaluation; Histamine H2 Antagonists; Humans; Peptic Ulcer; Piperidines

The first H2-receptor antagonist, cimetidine, has been succeeded by ranitidine, and more recently nizatidine and famotidine. Others will doubtless follow. The pharmacodynamic differences between cimetidine and ranitidine, in terms of potency, are not obviously translated into therapeutic differences. Some studies have shown that the increased potency of standard doses of ranitidine affords an advantage, in terms of ulcer healing and relapse, over cimetidine. The therapeutic effects of these drugs can be predicted from their pharmacodynamic profiles and in the doses recommended differences between the newest agents and ranitidine would not be expected. It is, thus, difficult to define a specific clinical role for the newer drugs on the grounds of efficacy. Their importance may relate to the provision of encouragement for future drug development.

Topics: Animals; Famotidine; Histamine H2 Antagonists; Humans; Nizatidine; Peptic Ulcer; Piperidines; Thiazoles

Possible mechanisms of drug interactions with H2-antagonists are outlined. The mode of action of roxatidine acetate on hepatic microsomal enzymes is contrasted with those of cimetidine and ranitidine, and their differing structure-activity relationships are discussed. In the light of the mechanisms of drug interactions with H2-antagonists, clinical studies with roxatidine acetate are contrasted with published interaction data of cimetidine and ranitidine. The therapeutic consequences of these data are considered.

Topics: Anti-Ulcer Agents; Cimetidine; Drug Interactions; Histamine H2 Antagonists; Humans; Peptic Ulcer; Piperidines; Ranitidine; Structure-Activity Relationship

In this randomized single-blind cross-over study the gastroduodenal damaging effect of indometacin 75 mg bid alone and in combination with roxatidine acetate (CAS 78628-28-1, Roxit) 75 mg nocte or 75 mg bid was evaluated in 12 healthy male volunteers. Prior to the start of the three therapeutic periods subjects underwent endoscopic examination to exclude gastroduodenal mucosa lesions. On days 7 and 14 of therapy 2 h after the application of the last indometacin dose subjects underwent endoscopy again. The 7- and 14-days administration of indometacin 75 mg bid, indometacin 75 mg bid plus roxatidine 75 mg nocte and indometacin 75 mg bid plus roxatidine 75 mg bid led to gastroduodenal mucosa lesion scores of 1.67 +/- 0.40 and 2.00 +/- 0.35, 1.33 +/- 0.28 and 1.50 +/- 0.29, 0.42 +/- 0.23 and 1.00 +/- 0.33 (mean +/- SEM), respectively. These differences were statistically significant when comparing indometacin 75 mg bid versus indometacin 75 mg bid plus roxatidine 75 mg bid (p < 0.004 and < 0.008, respectively). This study shows that roxatidine acetate represents an effective alternative in the prophylaxis of NSAID-induced gastroduodenal mucosa lesions.

Topics: Adult; Cross-Over Studies; Histamine H2 Antagonists; Humans; Indomethacin; Male; Peptic Ulcer; Piperidines; Single-Blind Method

This study reports preliminary results of a controlled, multicenter trial on the quality of ulcer healing induced by lansoprazole (LPZ) or roxatidine (R) in gastric ulcer (GU) or duodenal ulcer (DU) patients. Group A received LPZ 30 mg q.d. and group B received R 75 mg b.i.d. All drugs were given for 8 weeks in GU and for 6 weeks in DU. Endoscopy and gastric biopsy were performed to detect Helicobacter pylori before and on completion of treatment. The healing rates of groups A and B were 100 and 69.2%, respectively, in GU and 100 and 70.0%, respectively, in DU. This difference (p < 0.01) was significant between the two groups in GU. There was no significant difference between the two groups in the S2 stage shift rate in GU and DU. The H. pylori clearance rates of groups A and B were 33.3 and 20.0%, respectively, in GU and 62.5 and 33.3%, respectively, in DU. The differences in treatment response (healing rates and S2 shift rates) between the LPZ group and the R group may be related to the differences in suppression of acid secretion and in bactericidal effects on H. pylori.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Duodenal Ulcer; Female; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Peptic Ulcer; Piperidines; Proton Pump Inhibitors; Stomach Ulcer

Topics: Adolescent; Adult; Aged; Cimetidine; Female; Histamine H2 Antagonists; Humans; Male; Middle Aged; Peptic Ulcer; Piperidines

The effects of a new H2-receptor antagonist, roxatidine acetate, have been investigated in both clinical and pharmacodynamic trials in Europe and the United States. A series of four double-blind randomized studies are reviewed, reporting the effects of different dose regimens of roxatidine acetate compared with ranitidine and placebo in healthy volunteers using continuous intragastric pH monitoring. These pharmacodynamic studies clearly demonstrate that roxatidine acetate is an effective gastric antisecretory agent, which is up to twice as potent as ranitidine. The results of several clinical studies of roxatidine acetate in patients with gastric as well as duodenal ulcer conducted in Europe, Japan, and the United States are also reviewed. These studies show that roxatidine acetate is comparable to other potent H2-receptor antagonists in terms of cumulative healing rates, pain relief, and safety. Overall, the pharmacodynamic and clinical data indicate that the efficacy of roxatidine acetate 75 mg twice-daily (b.i.d.) does not differ significantly from ranitidine 150 mg b.i.d. Roxatidine acetate is equally effective in the treatment of peptic disease including gastric ulcer, duodenal ulcer, and reflux esophagitis.

Topics: Cimetidine; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Histamine H2 Antagonists; Humans; Peptic Ulcer; Piperidines; Random Allocation; Ranitidine

Roxatidine acetate is a novel H2-receptor antagonist with a chemical structure different to the earlier drugs of this type. It is a potent inhibitor of histamine-mediated gastric acid secretion and in animal models is 4 to 6 times as potent as cimetidine. In a multicentre double-blind clinical trial of over 700 patients with gastric or duodenal ulcers roxatidine acetate 75 mg twice daily and cimetidine 200mg four times daily produced endoscopically confirmed and subjective and objective healing rates in excess of 90% for both types of ulcer, with no significant difference between the treatments. Roxatidine acetate's efficacy in stomal ulcer (marginal ulcer) and reflux oesophagitis has been confirmed in non-comparative studies of up to 8 weeks' duration. The overall incidence of adverse reactions in 1623 patients treated with roxatidine acetate 75 mg twice daily was 1.7%, with skin rashes and constipation the most frequently reported side effects.

Topics: Adult; Cimetidine; Duodenal Ulcer; Female; Gastrins; Histamine H2 Antagonists; Humans; Japan; Male; Middle Aged; Pepsinogens; Peptic Ulcer; Piperidines; Prolactin; Stomach Ulcer; Time Factors

The effect of cisapride, 10 mg three times daily, was evaluated in a double-blind randomized study in 118 patients with non-ulcer dyspepsia. Peptic ulcer disease was excluded by endoscopy, gallstones by ultrasonography, and chronic pancreatitis by a series of non-invasive tests. Symptomatic improvement was evaluated by interview after 2 and 4 weeks; the patients also kept a diary. Cisapride caused significant improvement compared with placebo with regard to frequency and severity of symptoms and may therefore be useful in the therapy of non-ulcer dyspepsia.

Topics: Cisapride; Clinical Trials as Topic; Double-Blind Method; Dyspepsia; Humans; Peptic Ulcer; Piperidines; Random Allocation

Topics: Antidiarrheals; Clinical Trials as Topic; Diarrhea; Duodenitis; Gastroenteritis; Humans; Loperamide; Peptic Ulcer; Piperidines

Prostaglandin E2 (PGE2), one of the terminal products in the cyclooxygenase pathway, plays an important role in various inflammatory responses. To determine whether selective inhibition of PGE2 may relieve these inflammatory symptoms, we synthesized a selective PGE2 synthesis inhibitor, compound A [1-(6-fluoro-5,7-dimethyl-1,3-benzothiazol-2-yl)-N-[(1S,2R)-2-(hydroxymethyl)cyclohexyl]piperidine-4-carboxamide], then investigated the effects on pyrexia, arthritis and inflammatory pain in guinea pigs. In LPS-stimulated guinea pig macrophages, compound A selectively inhibited inducible PGE2 biosynthesis in a dose-dependent manner whereas enhanced the formation of thromboxane B2 (TXB2). Compound A suppressed yeast-evoked PGE2 production selectively and enhanced the production of TXB2 and 6-keto PGF1αin vivo. In addition, compound A relieved yeast-induced pyrexia and also suppressed paw swelling in an adjuvant-induced arthritis model. The effect on gastrointestinal (GI) ulcer formation was also evaluated and compound A showed a lower GI adverse effect than indomethacin. However, compound A failed to relieve yeast-induced thermal hyperalgesia. These results suggest that selective inhibition of PGE2 synthesis may have anti-pyretic and anti-inflammatory properties without GI side effect, but lack the analgesic efficacy.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Benzothiazoles; Depression, Chemical; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Fever; Guinea Pigs; Imidazoles; Indomethacin; Inflammation; Macrophages; Pain; Peptic Ulcer; Phenanthrenes; Piperidines; Stimulation, Chemical; Thromboxane B2

To evaluate gastrointestinal (GI) perforation in rheumatoid arthritis (RA) patients receiving tofacitinib, tocilizumab, or other biologic agents.. Using health plan data from 2006 through 2014, RA patients without prior GI perforation were identified. Those in whom treatment with tofacitinib or a biologic agent was being initiated were followed up for incident GI perforation with hospitalization. Crude incidence rates were calculated by exposure. Adjusted Cox proportional hazards models were used to evaluate the association between GI perforation and exposures. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated.. A cohort of 167,113 RA patients was analyzed. Among them, 4,755 began treatment with tofacitinib, 11,705 with tocilizumab, 115,047 with a tumor necrosis factor inhibitor (TNFi), 31,214 with abatacept, and 4,392 with rituximab. Compared to TNFi recipients, abatacept recipients were older, tofacitinib and rituximab recipients were younger, and tocilizumab recipients were similar in age. Patients beginning treatment with a non-TNFi agent were more likely to have previously received biologic agents than patients beginning treatment with a TNFi. The incidence of GI perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.55 (tocilizumab), 1.07 (abatacept), 0.73 (rituximab), and 0.83 (TNFi). Most perforations occurred in the lower GI tract: the incidence of lower GI tract perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.26 (tocilizumab), 0.76 (abatacept), 0.48 (rituximab), and 0.46 (TNFi). Lower GI tract perforation risk was significantly elevated with tocilizumab treatment, and numerically elevated with tofacitinib treatment, versus treatment with TNFi. Adjusted HRs were 2.51 (95% CI 1.31-4.80) for tocilizumab and 1.94 (95% CI 0.49-7.65) for tofacitinib. Older age (HR 1.16 per 5 years [95% CI 1.10-1.22]), diverticulitis/other GI conditions (HR 3.25 [95% CI 1.62-6.50]), and prednisone use at >7.5 mg/day (HR 2.29 [95% CI 1.39-3.78]) were associated with lower GI tract perforation. The incidence of upper GI tract perforation was similar among all drug exposures.. The risk of lower GI tract perforation associated with tocilizumab treatment, and possibly tofacitinib treatment, is elevated compared to that associated with TNF blockade.

Topics: Abatacept; Adult; Age Factors; Aged; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Databases, Factual; Diverticulitis; Esophageal Perforation; Female; Gastroesophageal Reflux; Glucocorticoids; Humans; Incidence; Intestinal Perforation; Male; Medicare; Middle Aged; Peptic Ulcer; Piperidines; Prednisone; Proportional Hazards Models; Pyrimidines; Pyrroles; Risk Factors; Rituximab; Tumor Necrosis Factor-alpha; United States

We examined the effect of lafutidine, a histamine H(2) receptor antagonist with a mucosal protective action mediated by capsaicin-sensitive sensory neurons (CSN), on intestinal lesions produced by loxoprofen administration in rats.. Animals were given loxoprofen (10-100 mg/kg p.o.) and killed 24 h later. Lafutidine (10 and 30 mg/kg), cimetidine (100 mg/kg) or famotidine (30 mg/kg) was given twice p.o. at 0.5 h before and 6 h after loxoprofen. Omeprazole (100 mg/kg) was given p.o. once 0.5 h before. Ampicillin (800 mg/kg) was given p.o. twice at 24 h and 0.5 h before loxoprofen, while 16,16-dimethyl prostaglandin E(2) (dmPGE(2); 0.01 mg/kg) was given i.v. twice at 5 min before and 6 h after.. Loxoprofen dose-dependently produced hemorrhagic lesions in the small intestine, accompanied by invasion of enterobacteria and increased inducible nitric oxide synthase (iNOS) expression as well as myeloperoxidase activity in the mucosa. The ulcerogenic response to loxoprofen (60 mg/kg) was significantly prevented by lafutidine (30 mg/kg), similar to dmPGE(2) and ampicillin, and the effect of lafutidine was totally attenuated by ablation of CSN. Neither cimetidine, famotidine nor omeprazole had a significant effect against these lesions. Lafutidine alone increased mucus secretion and reverted the decreased mucus response to loxoprofen, resulting in suppression of bacterial invasion and iNOS expression. In addition, loxoprofen downregulated Muc2 expression, and this response was totally reversed by lafutidine mediated by CSN.. Lafutidine protects the small intestine against loxoprofen-induced lesions, essentially mediated by the CSN, and this effect may be functionally associated with increased Muc2 expression/mucus secretion, an important factor in the suppression of bacterial invasion.

Topics: 16,16-Dimethylprostaglandin E2; Acetamides; Ampicillin; Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Capsaicin; Cimetidine; Disease Models, Animal; Enterobacteriaceae; Famotidine; Histamine H2 Antagonists; Intestinal Mucosa; Intestine, Small; Male; Mucin-2; Nitric Oxide Synthase Type II; Omeprazole; Peptic Ulcer; Peroxidase; Phenylpropionates; Piperidines; Proton Pump Inhibitors; Pyridines; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sensory Receptor Cells

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most significant causative factors of gastroduodenal ulcers. Recent reports have demonstrated that NSAIDs can also frequently induce ulceration and erosions of the small intestine. The aim of this study was to examine whether or not roxatidine (an H(2) receptor antagonist), which is known to increase gastric mucus in addition to inhibiting gastric acid, might suppress indomethacin-induced small intestinal mucosal injury, through an increase in mucus in rats.. Rats were given two p.o. doses of roxatidine, famotidine or cimetidine before and after the s.c. indomethacin injection. The injured area of the small intestine was analyzed. To examine effects of drugs on small intestinal mucus, rats were also given two p.o. doses of roxatidine, famotidine or cimetidine, and the ratio of the periodic acid Schiff (PAS)-positive area to the area of the mucosa in the small intestine was analyzed. In addition, we evaluated the involvement of nitric oxide (NO) and prostaglandins (PG) in the effect of roxatidine on small intestinal mucus.. Roxatidine significantly ameliorated indomethacin-induced small intestinal injury and increased the PAS-stained areas in the small intestinal mucosa, while cimetidine and famotidine had no significant effect. Pretreatment with N-nitro-L-arginine methyl ester but not with indomethacin, suppressed the effect of roxatidine on small intestinal mucus, suggesting that the effect is mediated by endogenous NO but not by PG.. Roxatidine suppressed indomethacin-induced small intestinal injury in rats. One possible mechanism is an increase of small intestinal mucus, mediated by NO.

Topics: Animals; Anti-Ulcer Agents; Cimetidine; Disease Models, Animal; Famotidine; Histamine H2 Antagonists; Indomethacin; Intestinal Mucosa; Intestine, Small; Male; Mucus; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Peptic Ulcer; Piperidines; Prostaglandins; Rats; Rats, Sprague-Dawley

Patients with liver disease are prone to develop peptic ulceration and often receive H(2)-receptor antagonists. Therefore, it is important to clarify whether the pharmacokinetics of H(2)-receptor antagonists is affected by hepatic function. However, pharmacokinetics of a new H(2)-receptor antagonist, roxatidine acetate, in chronic liver disease has not been well known. In this study, we analyzed the pharmacokinetics of roxatidine in patients with liver disease.. Blood samples were obtained from 11 patients with chronic hepatitis, 11 patients with cirrhosis and six healthy subjects. Under fasting conditions, 75 mg of roxatidine acetate was administered orally, and plasma roxatidine levels were determined sequentially from 3 to 12 h. Relationships between pharmacokinetic variables and each parameter related to hepatic functions were also investigated.. There was no difference in the pharmacokinetic variables and serum levels of roxatidine between chronic hepatitis and healthy controls. In contrast, in cirrhosis, serum roxatidine levels were significantly higher than those in chronic hepatitis and normal control. Half-life, the area under the plasma concentration-time curve and clearance in cirrhosis were also significantly longer, bigger and smaller than those in chronic hepatitis and healthy controls, respectively. The half-life became longer and the clearance became smaller in parallel with the progression of liver disease. Serum levels of hyaluronate and gamma-glutamyl transpeptidase showed a good correlation with half-life, clearance and elimination rate. A good correlation between creatinine clearance and elimination rate was found.. Pharmacokinetics of roxatidine acetate is affected by hepatic function, and the dosage of roxatidine acetate for patients with liver disease, especially cirrhosis, should be modified.

Topics: Administration, Oral; Adult; Aged; Area Under Curve; Chronic Disease; Creatinine; Half-Life; Hepatitis C, Chronic; Histamine H2 Antagonists; Humans; Liver Cirrhosis; Liver Function Tests; Metabolic Clearance Rate; Middle Aged; Peptic Ulcer; Piperidines

We have studied the effect of the newly synthesized agent MX1, a salt of the active metabolite of the H2-blocker roxatidine with a complex of bismuth and citric acid (N-[3-(3-(1-piperidinylmethyl)phenoxy)propyl]-hydroxyacetamide+ ++ -2-hydroxypropane-1,2,3-tricarboxilate-bismuth(3+) complex), against restraint stress ulcers in rats (24 h immobilization). The effects of MX1 (12.5, 50, 125, 184 and 250 mg kg-1) were compared with the effects of equimolar doses of roxatidine (6.5, 25, 70, 100 and 140 mg kg-1) and bismuth subcitrate (6.5, 25, 70, 100 and 140 mg kg-1). The results show that MX1-pre-treatment, at all the doses used, significantly reduces the mean number and size of ulcers. Even at the lowest dose the number of ulcers was reduced by 64.3% and the size of the ulcer by 55.9%. Roxatidine (25, 70, 100 and 140 mg kg-1) dose-dependently reduces ulcer size and number by 24.6, 55.6, 85.3 and 89.0% and by (+7.2), 14.3, 57.1 and 67.9%, respectively. Bismuth subcitrate significantly reduces ulcer size and number only at the highest dose employed (-28.5 and -44.8%, respectively). The morphometric results have been confirmed histomorphologically. The results suggest that MX1 has a gastroprotective effect against stress-induced ulcers which is similar to that of the parent compound and more pronounced than that of bismuth subcitrate.

Topics: Animals; Antacids; Anti-Ulcer Agents; Drug Combinations; Gastric Mucosa; Histamine H2 Antagonists; Male; Organometallic Compounds; Peptic Ulcer; Piperidines; Rats; Rats, Wistar; Restraint, Physical

A 60-year-old male had visited our hospital periodically, because of perennial moderate atopic asthma, since 53 years of age. His symptoms had stabilized following treatment with oral theophylline 400 mg, tranilast 300 mg and inhalation of beclomethasone dipropionate 400 micrograms and procaterol hydrochloride. His peak expiratory flow rate early in the morning was 465 L/min, %VC was 115% and FEV1.0% was 62.4% in May of 1993. On May 24, 1993, though he had no gastrointestinal symptoms, gastrointestinal fiberscopy revealed a hiatal hernia, reflux esophagitis and active gastroduodenal ulcer. The upper gastrointestinal x-ray films showed gastroesophageal reflux. Therefore, we diagnosed bronchial asthma associated with reflux esophagitis and gastroduodenal ulcer. He was started on omeprazole, as a proton pump inhibitor (PPI), and cisapride. After the treatment with PPI and cisapride, his peak expiratory flow rate early in the morning and in the evening, %VC and FEV1.0 increased. Three months later gastrointestinal fiberscopy revealed improvement in the reflux esophagitis and the gastroduodenal ulcer. We speculate that the improvement in the peak expiratory flow rate is related to that of the gastroesophageal reflux.

Topics: Asthma; Cisapride; Esophagitis, Peptic; Humans; Male; Middle Aged; Omeprazole; Peak Expiratory Flow Rate; Peptic Ulcer; Piperidines

We examined the effects of a new compound, N-[3-[3-(piperidinomethyl)phenoxy]-propyl]-2-(2-hydroxyethyl-1- thio)acetamido.2-(4-hydroxy benzoyl)benzoate (Z-300), on the histamine H2-receptor, gastric secretion in rats and dogs, and acute gastro-duodenal lesions or chronic gastric ulcers in rats. Roxatidine acetate hydrochloride (roxatidine), a known histamine H2-receptor antagonist, was used as a reference compound. The pA2 values for Z-300 and roxatidine for the isolated guinea pig atrium were 6.8 and 7.0, respectively. These agents at less than 10(-5) M did not affect the contraction of guinea pig ileum in response to carbachol. Z-300, administered either orally or parenterally, significantly inhibited the basal and histamine-stimulated gastric acid secretion in rats. Gastric acid secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain pouch dogs was also significantly inhibited by the compound. The effect persisted for greater than 7 hr in the case of histamine-stimulation. Oral Z-300 significantly protected the gastric mucosa from water-immersion stress-, indomethacin-, aspirin- and HCl.ethanol-induced lesions and protected the duodenal mucosa against mepirizole- and cysteamine-induced ulcers. These effects on gastric secretion and lesion formation were, as a whole, stronger than those observed with roxatidine. Z-300, but not roxatidine, significantly accelerated the spontaneous healing of acetic acid ulcers induced in rats and prevented the delay in ulcer healing caused by indomethacin. The mechanism of action of Z-300 on acute lesions and chronic ulcers appears to be mostly related to its potent antisecretory and mucosal-protective activities.

Topics: Acetamides; Administration, Oral; Animals; Dogs; Duodenum; Female; Gastric Acid; Gastric Mucosa; Histamine H2 Antagonists; Male; Peptic Ulcer; Piperidines; Rats; Rats, Inbred Strains; Stomach; Stomach Ulcer

Effects of some drugs modulating central histaminergic (HA) transmission were evaluated on restraint stress (RS)-induced gastric ulcerogenesis, plasma corticosterone and immune responses in rats. RS for (i) 6 hr or (ii) 24 hr at room temperature, and (iii) 3 hr at 4 degrees C (CRS) all induced gastric mucosal erosions and elevated plasma corticosterone levels, the effects with the latter two RS procedures being most consistent. Pretreatment of rats with neuronal HA depletor, alpha-FMH (100 mg/kg, ip) attenuated both ulcer severity and corticosterone response, during both 24 hr RS and CRS. Similar effects were also seen with the mast cell degranulator, C-48/80 (10 micrograms/kg, i.c.v.) treatment. Further, the H1-blocker, pheniramine (25 mg/kg, ip) but not the centrally acting H2-blocker, zolantidine (5 mg/kg, ip) produced clearcut attenuations in both stress markers, during the experimental stressors. In rats immunized in SRBC, 24 hr RS (and not CRS) significantly prevented the humoral immune responses to the antigen. alpha-FMH, C 48/80 and pheniramine but not zolantidine, reversed this response during 24 hr RS. The results indicate a central HA ergic involvement in the visceral, endocrinal and immune responses during RS and suggest the probable role of both neuronal as well as extraneuronal (mast cell) HA and activation of H1-receptors in the mediation of these effects.

Topics: Animals; Antibody Formation; Benzothiazoles; Brain; Corticosterone; Histamine; Histamine H2 Antagonists; Histidine Decarboxylase; Male; Methylhistidines; Peptic Ulcer; Pheniramine; Phenoxypropanolamines; Piperidines; Rats; Rats, Wistar; Stress, Physiological; Thiazoles

Topics: Acetylcholine; Cisapride; Dyspepsia; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Peptic Ulcer; Piperidines; Serotonin Antagonists

Topics: Drug Resistance; Histamine H2 Antagonists; Humans; Peptic Ulcer; Piperidines

The outstanding success of H2-blocking agents in ulcer therapy proves gastric acid as a dominating factor in the pathogenesis of ulcers. Motility disturbances can be demonstrated in ulcer patients but up to now in therapeutic terms played only a minor role. The therapeutic success of the antimuscarinic drug pirenzepine which inhibits only gastric secretory volume without influencing gastric pH but exerting a significant influence on interdigestive motility of the upper gastrointestinal tract reestablishes this factor to be of pathogenetic relevance. The pathophysiological factor of motility disturbances in the etiology of gastric ulcers is stressed also by the results of a recent therapeutic study comparing ranitidine and cisapride, where the motility-stimulating benzamide showed exactly the same rate of success as the H2-blocker; this holds true for both healing rate and symptomatic improvement. Therefore as far as chronic gastric ulcer is concerned a combination therapy should be preferred thus avoiding the side-effects of a strong and long lasting suppression of gastric acid secretion.

Topics: Cisapride; Gastrointestinal Motility; Humans; Metoclopramide; Peptic Ulcer; Piperidines; Pirenzepine; Ranitidine

Topics: Adult; Asian People; Benzyl Compounds; Gastric Juice; Humans; Male; Middle Aged; Parasympatholytics; Peptic Ulcer; Piperidines; Singapore

Topics: Animals; Male; Models, Chemical; Peptic Ulcer; Piperidines; Rats

Topics: Adult; Aged; Benzilates; Female; Fluphenazine; Humans; Male; Middle Aged; Peptic Ulcer; Piperidines; Quaternary Ammonium Compounds; Tranquilizing Agents

Topics: Animals; Bromides; Electric Stimulation; Fumarates; Gastric Juice; Gastrointestinal Motility; Guinea Pigs; Muscle, Smooth; Parasympathetic Nervous System; Parasympatholytics; Peptic Ulcer; Piperidines; Rats; Salivation; Stomach; Valerates

Topics: Adult; Alkynes; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Parasympatholytics; Peptic Ulcer; Piperidines

Topics: Atropine; Glucose; Mydriatics; Parasympatholytics; Peptic Ulcer; Pharmacology; Piperidines; Rats; Research; Ulcer

Topics: Benzilates; Parasympatholytics; Peptic Ulcer; Piperidines

Topics: Animals; Anti-Allergic Agents; Histamine H1 Antagonists; Peptic Ulcer; Piperidines; Rats; Reserpine; Serotonin; Stomach Ulcer

Topics: Gastroenterology; Gastrointestinal Diseases; Peptic Ulcer; Piperidines

Topics: Duodenal Ulcer; Humans; Peptic Ulcer; Piperidines

Topics: Cardiovascular Agents; Muscle Relaxants, Central; Peptic Ulcer; Piperidines

Topics: Cholinergic Antagonists; Humans; Parasympatholytics; Peptic Ulcer; Piperidines; Scopolamine Derivatives

Topics: Acetates; Cholinergic Antagonists; Humans; Parasympatholytics; Peptic Ulcer; Piperidines

Topics: Duodenal Ulcer; Parasympatholytics; Peptic Ulcer; Piperidines

Topics: Diet; Parasympatholytics; Peptic Ulcer; Piperidines; Sulfuric Acid Esters

Topics: Disease Management; Duodenal Ulcer; Parasympatholytics; Peptic Ulcer; Piperidines

Topics: Gastrointestinal Diseases; Parasympatholytics; Peptic Ulcer; Piperidines

Topics: Follow-Up Studies; Parasympatholytics; Peptic Ulcer; Piperidines; Ulcer

Topics: Methantheline; Parasympatholytics; Peptic Ulcer; Piperidines; Quaternary Ammonium Compounds

Topics: Cholinergic Antagonists; Disease; Duodenum; Gastritis; Humans; Parasympatholytics; Peptic Ulcer; Piperidines; Stomach Diseases

Topics: Digestion; Gastric Juice; Parasympatholytics; Peptic Ulcer; Piperidines

Topics: Cholinergic Antagonists; Endocarditis; Endocarditis, Subacute Bacterial; Humans; Peptic Ulcer; Piperidines

Topics: Parasympatholytics; Peptic Ulcer; Piperidines

Topics: Ammonium Compounds; Cell Movement; Parasympatholytics; Peptic Ulcer; Piperidines

Topics: Methantheline; Peptic Ulcer; Piperidines; Quaternary Ammonium Compounds