piperidines and bismuth-tripotassium-dicitrate

Topics: Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Omeprazole; Organometallic Compounds; Piperidines; Roxithromycin

Fifty-three patients with previously uninvestigated chronic dyspepsia symptoms in the absence of gastrointestinal or extra-gastrointestinal disease (functional dyspepsia) underwent antral and duodenal mucosal biopsies to detect the role of such samplings in the presence of normal endoscopic findings. Patients were enrolled in a randomized, placebo-controlled, double-blind trial, receiving either eradicating treatment (colloidal bismuth subcitrate plus metronidazole) or placebo if they had Helicobacter pylori-associated gastritis (20 patients), or cisapride or placebo if they had normal antral mucosa (28 cases). Unsuspected celiac sprue was found in one patient. Eradicating treatment ameliorated histological gastritis (p = 0.01). However, owing to great placebo efficacy, symptom remission rates following a 1-month wash-out period in both treatment groups were no higher than that in controls. Independent of the initial randomization, an extremely low symptom recurrence rate was observed during a drug-free follow-up study equivalent to the mean duration of symptoms before enrollment. We conclude that in functional dyspepsia, bulbar and antral biopsies are not useful in clinical management, equivalent symptom relief can be achieved in patients randomly assigned to both drugs and placebos, and such improvement can be long lasting in the absence of any maintenance treatment. We believe the prevalence of unsuspected villous atrophy and the therapeutic role of investigation-based reassurance deserve further assessment.

Topics: Adult; Anti-Bacterial Agents; Anti-Ulcer Agents; Biopsy; Bismuth; Cisapride; Double-Blind Method; Duodenum; Dyspepsia; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Piperidines; Pyloric Antrum

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