Lack of effect of domperidone on gastrin release: evidence for a peripheral activity of the drug.

The effect of intravenous administration of domperidone, a dopamine receptor antagonist with peripheral activity, on basal and submaximal pentagastrin-stimulated gastric acid secretion and gastrin release has been evaluated in healthy volunteers. No significant changes were observed in the parameters studied. The lack of effect on gastrin release appears to confirm that domperidone is unable to penetrate the blood brain barrier in appreciable amounts in adults.

Lack of effect of cimetidine on the renin-angiotensin-aldosterone system in man.

It is widely accepted that angiotensin II, ACTH and potassium are the major factors controlling the release of aldosterone. Conflicting results have been reported about the role of serotonin, dopamine and histamine. To evaluate the possible involvement of H2-histaminergic receptors, the effect of intravenous injection of 400 mg cimetidine on the renin-angiotensin-aldosterone system has been evaluated in 10 healthy volunteers. The administration of cimetidine did not induce a significant change in plasma aldosterone level or in its major controlling factors.

Dopaminergic control of gastric acid and gastrin secretion in man: lack of effects after acute oral administration of ibopamine, an analogue of dopamine.

The effect of oral administration of the dopaminergic drug, ibopamine, at the dose of 200 mg and 400 mg, on basal and submaximal pentagastrin (0.25 microgram kg-1 h-1) stimulated gastric acid secretion as well as basal serum gastrin concentration has been evaluated in 24 healthy individuals. In comparison with placebo no significant changes were observed in all the variables studied. The lack of effects on gastric acid secretion might be due to a selective stimulation of dopaminergic receptors not active in the regulation of gastric acidity or not present in gastric mucosa, while unchanged serum gastrin secretion is possibly due to a poor crossing of blood-brain barrier by ibopamine.

Effect of sulpiride isomers on gastric acid and gastrin secretion in healthy man.

The effects of the antidopaminergic drug sulpiride on gastric acid secretion and gastrin release have been evaluated in 42 healthy individuals. Basal and submaximal pentagastrin (0.5 micrograms/kg-h)-stimulated gastric acid secretion, as well as basal and meal-induced gastrin secretion, were studied after acute intramuscular administration of racemic sulpiride (100 mg) and its L-(50 mg) D-(50 mg) isomers. Racemic and L-sulpiride significantly decreased stimulated serum gastrin concentration, but they did not affect fasting serum gastrin or basal and stimulated gastric acidity. D-sulpiride significantly decreased gastric acid secretion, without affecting serum gastrin levels. While the effects of racemic and L-sulpiride are analogous to those of other antidopaminergic drugs, D-sulpiride mimics the action of dopamine, at least at gastric level. These data support the hypothesis that the D-isomer may possess agonist-antagonist activity at dopamine receptors. Since racemic sulpiride has been used with conflicting results in the therapy of patients with peptic ulcer, in the light of the present results it would be of interest to study separately the efficiency of the D- and L-isomers of the drug in healing peptic ulcer.

Effect of loperamide and naloxone on gastric acid secretion in healthy man.

The effect of acute oral administration of three different doses (4, 8, and 16 mg) of loperamide, a peripheral opiate agonist, on basal and submaximal pentagastrin-stimulated gastric acid secretion was evaluated in healthy volunteers. Both basal and stimulated gastric secretion were significantly lowered by 8 and 16 mg of the drug in comparison with a control study, while 4 mg was ineffective. Naloxone, a specific opiate antagonist, decreased slightly but not significantly both basal and pentagastrin-stimulated gastric acid secretion, when infused intravenously at the rate of 30 micrograms/kg/h, but completely abolished the inhibitory effect of loperamide on gastric acidity. These data also suggest that opiates may be involved in the regulation of gastric acid secretion in man by acting at a peripheral site, as loperamide does not cross the blood-brain barrier.

[Cimetidine: solution to a problem?]. / Cimetidina: soluzione di un problema?

Peptic ulcer is a widespread disease, the natural history which is long, painful and associated with high personal and social costs. Cimetidine is a highly effective and safe drug which, compared with the other treatments currently available, can be considered as the best solution of this problem.

Carbenoxolone maintenance in cimetidine-healed patients.

The effects of 3 months' maintenance treatments with cimetidine, 400 mg at bedtime, or with carbenoxolone, 150 mg/daily, in patients whose duodenal ulcers healed after an initial course with cimetidine were compared. Carbenoxolone promoted a significant enhancement of cimetidine-altered mucus secretion, whereas in the cimetidine group no mucus recovery was found. Within 6 months from healing time 48.1% of the patients in the cimetidine group relapsed, compared with 21.4% in the carbenoxolone group. The difference is statistically significant (p < 0.05). Our results suggest that carbenoxolone maintenance is more effective than cimetidine in preventing recurrence of ulcers, being also a cheaper and shorter maintenance treatment.

Effect of carbenoxolone and cimetidine on gastric mucin.

To determine whether the addition of carbenoxolone to a cimetidine regimen would prevent mucus deficiency in patients with duodenal ulcer, we compared the effect of combined therapy with the effects of treatment with cimetidine alone and carbenoxolone alone. Carbenoxolone proved to be ineffective on gastric mucus induced by cimetidine, the behavior of gastric mucin fractions being similar to that observed in patients treated with cimetidine alone. When used alone, however, carbenoxolone demonstrated mucus-stimulating action.

Prolactin release by intravenous cimetidine in man: evidence for a suprapituitary locus on action.

In an attempt to identify the sites at which cimetidine stimulates prolactin release, the drug was administered intravenously (6 mg/kg body weight) to healthy subjects under basal conditions, during dopamine infusion (1 microgram/Kg-min for 120 min) and after pretreatment with L-dopa plus carbidopa (250 plus 25 mg every 6 for 1 day). The serum prolactin response to cimetidine was abolished by dopamine infusion and almost completely suppressed by L-dopa plus carbidopa administration. These findings suggest that the drug acts on the central nervous system to stimulate prolactin release. Although the mechanism of this action is unclear, it does not seem to depend on an antidopaminergic effect and may be related to blackade of brain H2 histamine receptors.

Double blind comparison between cimetidine and gefarnate in cases of duodenal ulcer.

Thirty outpatients suffering from duodenal ulcer of recent onset were given cimetidine 1 g/day or gefarnate 250 mg/day for 6 weeks in a double blind trial, randomly balances between the groups. Endoscopic assessment was carried out at 4 and 6 weeks; patients healed after 4 weeks were withdrawn from the trial. In all parameters considered, cimetidine showed a highly significant difference. The healing rate at 4--6 weeks was 67--93% after cimetidine treatment and 27--53% after gefarnate treatment. The effect of cimetidine on the disappearance of symptoms, mainly the nocturnal ulcer pain, and on antacid consumption was greater than that after medication wity gefarnate. After 4--6 weeks of a full dose cimetidine regimen, both basal and pentagastrin stimulated gastric acid secretion were reduced and peptone meal stimulated serum gastrin increased; the basal gastrinaemia remained unchanged.

Stimulation of prolactin release by intravenous cimetidine: a dose-response study.

The PRL response to iv cimetidine was tested in 8 healthy males and 8 females at 4 different dose levels (0.75, 1.5, 3.0 and 6.0 mg/kg bw). Serum PRL levels were significantly increased in comparison with a placebo study by the second cimetidine dose in both sexes. The PRL response was significantly higher in females than in males at all but the lowest dose tested. A significant correlation between the cimetidine dose and the PRL response was observed. There was no significant modifications in serum GH, LH, FSH, IRI and glucose. Present findings demonstrate that the stimulation of PRL release by iv cimetidine is quite specific and dose-dependent.

Use of gentamicin to prevent intestinal side effects of lincomycin therapy.

Mild to severe and persisting diarrhea and even colitis have been reported as a side effect of therapy with lincomycin and clindamycin. An alteration in the normal bowel flora with an overgrowth of coliforms and other antibiotic-resistant bacteria has been postulated as a mechanism for the development of diarrhea. Investigations were undertaken in men to observe whether the simultaneous administration of gentamicin was capable of preventing lincomycin-associated intestinal disturbances. Of the 30 subjects treated only with lincomycin 11 (36.6%) developed diarrhea. Of the 18 subjects treated with lincomycin and simultaneously with oral gentamicine, none developed diarrhea. Results of bacteriological examinations indicate that in subjects treated with lincomycin, some potentially pathogenic bacteria, like coliforms and clostridia, are still present in intestinal flora; the simultaneous absence of bifidobacteria and bacteriodes could result in the abolishment of the host resistance to the noxious activity of these endogenous bacteria, as some reported data of the literature suggest. Coliforms and the majority of clostridia strains are not present in subjects treated simultaneously with gentamicin.

[Preliminary results of treatment with Tagamet (cimetidine SK and F) in gastric and duodenal ulcers]. / Primi risultati del trattamento con Tagamet (cimetidina SK & F) nelle ulcere gastriche e duodenali.

Following 3x200 mg Tagament (cymetidine SK & F) tablets at meals and 2 in the evening (5 per day) for an average of 31 days, complete endoscopic cure was obtained after 29 days (duodenal patients) and 35 days (gastric patients) in 26/27 subjects with slow healing histories (17 with duodenal and 10 with gastric ulcer). Rapid regression of pain and dyspepsia was observed form the outset and there was a marked reduction in the consumption of antacid preparation. Its marked efficacy and good tolerance make Tagamet a drug of choice in the treatment of peptic, duodenal and gastric ulcers.