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At least 19 recordsLinked to original sources
PubMed1976

The effect of metiamide, an H2-receptor antagonist, in the prevention of experimental stress ulcers.

Because of evidence that Metiamide, an H2-receptor antagonist, strongly inhibits gastric acid secretion, the present study was designed to test the hypothesis that Metiamide will prevent bile salt-induced stress ulcers during hemorrhagic shock. Forty dogs were bled and maintained for 4 1/2 hr at a mean blood pressure of 40 to 50 mm Hg. In group A, 10 dogs received 300 mg of Metiamide orally 45 min before bleeding and 10 dogs received normal saline. The pylorus was occluded before bleeding and 100 ml of 15 mM bile salt were instilled into the stomach and aspirated at the end of 4 1/2 hr. At the time the animal was killed after 48 hr, no ulcers were seen in the stomachs of dogs treated with Metiamide. Sixty per cent of the dogs in the untreated group developed multiple gross ulcers. In group B the effect of Metiamide on the disappearance rate of H+ ion was measured by instillation of 50 mM HCl + 15 mM bile acid. No difference was noted in the rate of H+ ion disappearance between Metiamide-treated and control dogs. Also, in 5 normotensive dogs the rate of H+ ion disappearance was measured before and after treatment with Metiamide, and the loss of H+ was identical for both periods. Metiamide was effective in preventing stress ulcer in this experimental model. The protective effect of Metiamide is probably due to its inhibitory effect of H+ ion secretion.

Administration, Oral↗
PubMed1975

Action of metiamide on the lower esophageal sphincter.

The action of metiamide, an H2 antagonist, was tested for its effect upon lower esophageal sphincter (LES) function in the anesthetized opossum. Intravenous infusions of metiamide gave a dose-related increase in LES pressure. A maximum increase in pressure of 17 mm Hg was attained at 2.0 mg per kg-hr of metiamide. This dose of metiamide abolished acid secretion in response to gastrin I, but augmented the maximal LES response to this hormone. Studies in vitro showed that metiamide augmented the maximal LES muscle responses to gastrin I or histamine but had no effect on other agonist responses. Metiamide alone did not alter LES muscle tension. An inhibitory response to gastrin I or histamine could be demonstrated in the presence of atropine or diphenhydramine, respectively, on muscle which had first been depolarized with KCl. These inhibitory responses were antagonized by metiamide. These studies indicate that metiamide: (a) increases LES pressure; (b) selectively augments LES muscle excitatory responses to gastrin I or histamine; and (c) selectively antagonizes inhibitory muscle responses to histamine or gastrin I.

Animals↗
PubMed1977

Metiamide and stimulated acid secretion from the isolated non-distended and distended mouse stomach.

1. The action of metiamide, a specific histamine H2-receptor antagonist, on the acid secretory response to various gastric stimuli in the perfused isolated whole mouse stomach is described. 2. Two kinds of stomach preparations, the non-distended stomach and distended stomach, were used. The distended stomach gave a marked and dose-related acid secretory response to histamine (10(-6) to 10(-3) M), pentagastrin (10(-8) to 10(-5) M), acetylcholine (5 X 10(-5) to 10(-5) M), eserine (10(-5) to 10(-3) M) to dibutyryl cyclic AMP (5 X 10(-5) to 10(-3) M). In the nondistended stomach, dibutyryl cyclic AMP regularly stimulated acid secretion in a dose-dependent manner; in contrast to dibutyryl cyclic AMP, histamine, pentagastrin or acetylcholine did not always stimulate acid secretion. 3. Histamine or pentagastrin but not acetylcholine always caused significant stimulation of acid secretion from the non-distended stomach in the presence of a phosphodiesterase inhibitor such as caffeine, theophylline or the I.C.I. compound, 63197. At the concentration of 10(-4) M, these phosphodiesterase inhibitors markedly potentiated the stimulatory effect of histamine or pentagastrin on acid secretion and the order of effectiveness was 63197 greater than theophylline greater than caffeine. 63197 also produced profound potentiation of histamine- or pentagastrin-stimulated acid secretion in the distended stomach. 4. Metiamide (5 X 10(-5) to 10(-4) M) did not antagonize stimulation of acid secretion by dibutyryl cyclic AMP in the non-distended or distended stomach. 5. In the distended stomach, metiamide (5 X 10(-4) M) produced significant inhibition of histamine-stimulated acid secretion with a linear and parallel displacement of the histamine dose--response curve to the right. Although at this concentration metiamide did not depress maximal acid secretory response to histamine, it caused marked reduction of the maximal acid secretory response attainable with pentagastrin. 6. In the distended stomach, metiamide (5 X 10(-5) M) did not cause significant inhibition of acetylcholine-induced acid secretion. Atropine (5 X 10(-6) M) abolished the stimulatory effect of acetylcholine; it also produced marked inhibition of pentagastrin-stimulated acid secretion but it had little effect on acid secretion induced by histamine. 7. The present results indicate that metiamide inhibited histamine-induced acid secretion by competitive antagonism of the histamine H2-receptor, but its inhibitory effect on pentagastrin-induced acid secretion seemed to be of non-competitive nature. The failure of metiamide to inhibit acid secretion induced by dibutyryl cyclic AMP suggests that cyclic AMP might regulate gastric acid secretion at a site beyond the histamine H2-receptor activation. It is also considered that the present results support the hypothesis that cyclic AMP may be involved in histamine- or pentagastrin-induced acid secretion in the isolated mouse stomach. 8...

Animals↗
PubMed1983

Effect of metiamide, a histamine H2-receptor antagonist on reserpine-induced gastric ulcers and acid secretion.

The effect of metiamide on reserpine-induced gastric ulcers and on gastric secretion during 6 h after ip administration was investigated in conscious intact rats and in rats with chronic gastric fistula. Reserpine, 3 mg/kg ip increased substantially the concentration of gastric acid in the first 4 h. Metiamide given every 3 h in a low dose (0.01 mumol/kg) intensified reserpine-induced gastric ulcers and also significantly increased the reserpine-induced acid concentration and output. In larger doses, (50-100 mumol/kg) metiamide considerably diminished gastric ulcer development and decreased gastric acid concentration. Given every 2 h metiamide in doses of 50-100 mumol/kg almost completely abolished gastric ulcer formation and markedly reduced the secretion of gastric acid in reserpinized rats. Anti-ulcer effect of metiamide was stronger than its antisecretory action, suggesting also the antiulcer action of metiamide other than inhibition of acid secretion. The results suggest that in conscious rats histamine H2-receptors are involved in reserpine-induced gastric ulcer development and gastric acid secretion. The antiulcer effect of metiamide may in part depend on its antisecretory action.

Animals↗
PubMed1975

Aspects of the effect of metiamide on pentagastrin-stimulated and basal gastric secretion of acid and pepsin in man.

This study has examined the inhibition produced by metiamide on the gastric secretion of acid and pepsin in 13 patients with duodenal and three with gastric ulcer. The effect of metiamide on the response to a range of doses of pentagastrin in three normal individuals was determined, as was the interaction of metiamide and atropine on prolonged basal secretion. Metiamide inhibited the secretion of acid more than pepsin and the gastric secretion of patients with gastric ulcer more than duodenal ulcer. Metiamide inhibited both the maximal secretory response attainable with pentagastrin and decreased the sensitivity to pentagastrin. Atropine augmented and prolonged the action of metiamide.

Atropine↗
PubMed1979

Effects of prolonged administration of metiamide on serum gastrin, gastrin content of the antrum and gastric corpus, and G-cell population in the rat.

The effect of prolonged metiamide administration on serum gastrin, gastrin content of the antrum and gastric corpus, and G-cell population was studied in the rat. A single subcutaneous injection of metiamide (200 mg/kg) at the onset of 16 days of continous treatment with three daily injections was followed by a fivefold increase in serum gastrin level at 4 hr in fasted and at 4 and 6 hr in fed rats. After 16 days of metiamide, the fed rats showed a peak in serum gastrin level of the same magnitude as on day 1, but only at 4 hr. Two hours later, the levels decreased rapidly to basal values. In the fasted animals, the response to metiamide was reduced to a threefold increase at 2 hr. There was no difference in gastrin content of the antrum and gastric corpus nor in volume density of the G-cells after the prolonged treatment compared with the controls. It is concluded that in spite of rises in serum gastrin, prolonged metiamide medication has no effect on the gastrin content of the antrum and gastric corpus nor on the G-cell population in the rat. Furthermore, after prolonged treatment, metiamide-induced gastrin release is diminished.

Animals↗
PubMed1976

Inhibition of basal and stimulated gastric H+ and pepsin secretion in duodenal ulcer patients by metiamide, an H-2 histamine antagonist.

Metiamide was given orally in one dose of 200 mg in 23 sutdies in patients with duodenal ulcer, 4 in the basal state, 11 during histamine infusion, and 8 before insulin hypoglycemia stimulation. In the latter 8 patients insulin was given at another time without metiamide. In 17 studies acid secretion was suppressed by metiamide--up to 75% in the basal state, 53% after histamine, and 80% after insulin. Pepsin secretion was reduced to the same extent as H+ in the histamine studies but not in the basal (57%) or insulin (44%) studies, so that in the latter pepsin/acid ratios were 3-fold greater than in controls. Blood levels of metiamide were measured in 17 studies. In 10 out of 11 who showed inhibition of 40% or more, peak blood levels of metiamide were 0.45 mug/ml to 1.25 mug/ml. In 5 of 6 who did not show inhibition, blood levels were 0.05-0.4 mug/ml; in the sixth it was 0.8 mug/ml. Therefore a critical blood level for suppression of basal or stimulated secretion appears to be approximately 0.45 mug/ml.

Adolescent↗
PubMed1981

Influence of metiamide and atropine on acid and pepsin secretion in the anaesthetized Heidenhain cat.

The inhibition of acid and pepsin secretion by metiamide and atropine was studied in the anaesthetized Heidenhain-pouch cat. Metiamide strongly inhibited acid secretion induced by histamine, pentagastrin or carbachol. Metiamide had not effect on pepsin secretion stimulated by pentagastrin and carbachol but was effective on histamine-stimulated pepsin secretion. Atropine strongly inhibited pepsin secretion but was not as effective as metiamide in the inhibition of acid secretion. Reperfusion of the pouch with acid + salicylic acid also increased pepsin secretion. This increased pepsin output was abolished by atropine, but not by metiamide. It is postulated that (1) the peptic cell probably has only cholinergic receptors which can be additionally triggered by HCl passing the peptic cell, and (2) H2-antagonists only inhibit pepsin secretion indirectly via reduction of acid output.

Anesthesia↗
PubMed1979

Inhibition of pepsin secretion by metiamide and atropine in the conscious rat.

The inhibition of pepsin secretion by metiamide and atropine has been studied in the gastric fistula rat and the Heidenhain pouch rat. A comparison of the effectiveness of metiamide and atropine in inhibiting pepsin secretion was made by using doses of the antagonists which produced a similar level of inhibition of acid secretion. In the gastric fistula rat both atropine and metiamide inhibited the basal pepsin output, but atropine was more effective than metiamide in this respect. In the Heidenhain pouch rat a large dose of metiamide which inhibited bethanechol-stimulated acid secretion had no significant effect on the corresponding output of pepsin. In this preparation atropine inhibited both acid and pepsin secretion. Possible reasons for the differences in the two preparations are discussed.

Animals↗
PubMedDate not supplied

The effects of metiamide on gastric secretion and stress ulceration in rats.

The effects of metiamide, a histamine H2 blocker, on gastric secretion and ulcer formation in stressed pylorus-occluded rats were investigated. Metiamide, like atropine, significantly reduced the volume of gastric secretion and total acid output in unrestrained pylorus-occluded rats. Both drugs produced greater decreases in the volumes of gastric secretion in stressed rats than in their corresponding unrestrained groups. Stress itself reduced both parameters. Metiamide, like atropine, significantly reduced the incidence of gastric stress ulcers. When given together these two drugs did not provide greater protection. The results obtained with metiamide indicate that histamine plays a role in basal gastric secretion and in the pathogenesis of stress ulcers. As no correlation between gastric acid secretion and ulcer formation was demonstrated in this study, it is suggested that H2 receptors may also be involved in gastric motility. However, the possibility that metiamide could exert its ulcer-protecting effects through other mechanisms cannot yet be excluded.

Animals↗
PubMed1975

Effects of metiamide on the human stomach.

1. The effect of metiamide on gastric acidity in man has been studied. Solutions of hydrochloric acid or glucose were instilled into the stomach and the subsequent rates of gastric secretion and emptying, and the disappearance of acid within the stomach, were measured. 2. Metiamide inhibited the gastric secretory response to the instilled acid and glucose solutions but did not change the overall pattern of emptying of the instilled solutions. 3. During administration of metiamide, there was a net loss of acid from within the gastric lumen. The rate of disappearance of acid from the instilled acid solution was small and not sufficient in magnitude to account for the metiamide-evoked decrease in the concentration of acid secreted in response to pentagastrin. 4. We conclude that metiamide does not inhibit gastric secretion by altering the 'barrier' function of the gastric mucosa.

Bile Pigments↗
PubMed1978

Inhibition by metiamide of secretagogue-induced gastric acid secretion in the conscious Heidenhain pouch rat.

1. The inhibition by metiamide of gastric of gastric acid secretion in response to histamine, pentagastrin and bethanechol has been investigated in the conscious Heidenhain pouch rat. 2. Histamine alone stimulated only a low rate of acid secretion. This response was markedly potentiated in the presence of mepyramine. 3. Metiamide at a dose of 0.15 mumole . kg-1 . min-1 I.V. significantly inhibited the acid secretory responses to histamine (in the presence of mepyramine) and pentagastrin. In each case the inhibition of acid output was the result of a significant decrease in both secretory volume and acid concentration. 4. Metiamide at a dose of 0.15 mumole . kg-1 . min-1 I.V. did not inhibit bethanechol-stimulated acid secretion. Increasing the dose of metiamide to 1.0 mumole . kg 1 . min-1 I.V. did produce a significant inhibition. In contrast with histamine and pentagastrin, metiamide inhibited bethanechol-stimulated secretion only by reducing acid concentration; there was no significant decrease in the gastric secretory volume. 5. It is concluded that these results are consistent with the view that histamine and pentagastrin share a common pathway in stimulating gastric acid secretion in the rat. The role of histamine in the control of bethanechol-stimulated acid secretion remains unclear.

Animals↗
PubMed1976

Effect of the histamine (H2) inhibitor metiamide on histamine-stimulated bile flow in dogs.

The effects of the histamine H2-receptor inhibitor metiamide on histamine-stimulated canine bile flow and gastric hydrogen ion output were evaluated. Histamine was found to stimulate bile volume in doses comparable to those that stimulated gastric hydrogen ion output; both responses appeared to have the same maximal response dose, 150 mug/kg per h. Metiamide alone did not alter hepatic bile flow. Administration of metiamide, 2 mg/kg per h, along with various doses of histamine demonstrated that the H2-receptor antagonist decreased bile volume and gastric hydrogen ion output from values obtained with histamine administration alone. The D50 of histamine for bile flow was 16.3 mug/kg per h and the D50 for hydrogen ion output was 44.2 mug/kg per h, Kinetic analysis suggests that the decrease in histamine-stimulated hydrogen ion output produced by metiamide is the result of competitive inhibition; the decrease in histamine-stimulated bile volume by metiamide which is different from the hydrogen ion inhibition, suggests noncompetitive inhibition. These data indicate that the mechanism of histamine choleresis is different from the mechanism of histamine-stimulated gastric acid output and that histamine-stimulated bile flow may not be the result of direct hormone-receptor interaction.

Animals↗
PubMed1977

Histamine receptors in the coronary circulation of the dog. Effects of mepyramine and metiamide on responses to histamine infusions.

The effect of histamine on coronary blood flow (CBF) was studied in anaesthetized grayhounds. CBF and systemic blood pressure were measured using electromagnetic flow transducers and catheters in the aorta during infusions of drugs into the left circumflex coronary artery. Histamine infusions (5, 10, and 20 microng/min) produced dose-related increases in CBF without changing heart rate or blood pressure. Metiamide (100 microng/min) given simultaneously produced a parallel displacement of the histamine dose-response curve to the right (P less than 0.05) with a dose ratio of 2. Mepyramine (100 microng/min) produced a larger parallel displacement of the dose-response curve (dose ratio = 4). Together, metiamide and mepyramine greatly reduced the histamine response (dose ratio = 16), showing that the metiamide blockade is augmented in the presence of mepyramine. Similarly, mepyramine blockade is augmented in the presence of metiamide. The increase in CBF produced by histamine infusion (20 microng/min) was similar to the peak flow response of reactive hyperemia following 8-second occlusions. However, mepyramine and metiamide together had no effect on the peak flow response, duration, or total repayment of flow debt in reactive hyperemia. These results show that histamine-induced coronary vasodilation is mediated by both H1 and H2 receptors. However, the vasodilation of reactive hyperemia after brief coronary artery occlusions does not appear to involve histamine.

Animals↗
PubMed1976

The pharmacology of burimamide and metiamide, two histamine H2-receptor antagonists.

Burimamide and metiamide are two histamine H2-receptor antagonists. Evidence is presented that indicates the competitive nature and the specificity of the antagonism. Metiamide is about ten times more potent than burimamide and is also more effective than burimamide when given orally. Both compounds inhibit gastric secretion and the evidence is consistent with this inhibition being due to competitive antagonism of H2 receptors in the gastric mucosa. Burimamide, unlike metiamide, causes release of catecholamines even at dose levels that are just sufficient to produce H2-receptor antagonism. Burimamide, but not metiamide, has alpha-adrenoceptor blocking activity. In certain models for inflammation, particularly rat paw edema induced by compound 48/80, burimamide in combination with the H1-receptor antagonist mepyramine shows anti-inflammatory activity. This may, in part, be associated with the catecholamine-releasing properties of the compound. Metiamide is less active in this respect.

Animals↗
PubMed1980

Metiamide potentiates the stimulant actions of sympathomimetic amines "in vitro".

Metiamide significantly potentiated the contractions of the guinea-pig and the rat vas deferens and seminal vesicle produced by noradrenaline, dopamine and methoxamine. The responses to acetylcholine and carbachol were not affected by metiamide. Tetrodotoxin did not affect metiamide-induced potentiation of the sympathomimetics. Potentiation induced by metiamide was Ca++-dependent. Mepyramine failed to influence the responses to the amines. It is suggested thaat extra-neuronal mechanisms may be involved in the interactions of metiamide and sympathomimetics.

Acetylcholine↗
PubMed1978

Metiamide: more than an H2-receptor antagonist.

The effect of metiamide on acid secretion and calcium uptake by the frog gastric mucosa was tested alone and in combination with histamine, pentagastrin, aminophylline, and dibutyrl cyclic AMP (db cAMP). Metiamide inhibited all stimulants including db cAMP which presumably acts intracellularly beyond the H2 receptor. Metiamide, therefore, actively inhibits at a point within the cell beyond the adenylated cyclase membrane receptor complexes. Metiamide also increases calcium influx into the parietal cell, suggesting yet another possible mechanism of inhibition.

Animals↗
PubMed1979

The effects of metiamide and H1 receptor blocking agents on anaphylactic response in guinea-pigs.

The effects of metiamide and of four H1 receptor blocking agents (mepyramine, promethazine, clemastine and ketotifene) on anaphylactic reaction were studied in the guinea-pig. The H1 blockers conferred partial protection which shows that with the experimental protocol utilized (challenge injection with high doses of antigen), histamine plays a lesser role than other mediators released or synthesized. Metiamide (30.0 mg/kg i.v.) noticeably enhanced the increase in pulmonary resistance observed during anaphylactic reaction and reduced the protective effect of the H1 antagonists on this parameter and on histamine release. These effects might be explained by an inhibition - at least partial - of the negative feed-back mechanism through which histamine controls its own release, or by a specific action of metiamide in high doses. The transient tachycardia initially observed in anaphylactic shock is partly related to stimulation of cardiac H2 receptors by the histamine released, since it is suppressed by metiamide.

Airway Resistance↗