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Results for “Histamine H2 Antagonists”

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At least 19 recordsLinked to original sources
PubMed1981

The use of H1 and H2 histamine antagonists with morphine anesthesia: a double-blind study.

High doses of morphine can produce significant cardiovascular effects generally attributed to histamine release. The authors examined the possibility that H1 and H2 histamine antagonists might prove beneficial in preventing these responses. In a randomized double-blind study, four groups of 10 patients each received 1 mg/kg morphine and either a placebo, diphenhydramine (H1), cimetidine (H2), or both of the histamine antagonists. The morphine-placebo group demonstrated a marked elevation in plasma histamine levels (880 +/- 163 to 7437 +/- 2684 pg/ml), a decrease in systemic vascular resistance (SVR) (15.5 to 9.0 l torr/(l . min-1) and diastolic BP (71 +/- 3 to 45 +/- 4 torr) and an increase in cardiac index (CI) (2.4 +/- 0.2 to 3.0 +/- 0.21 . min-1 . m-2). The administration of either cimetidine or diphenhydramine with morphine provided minimal protection. Those patients who received morphine and both antagonists demonstrated significant attenuation of these responses (CI 2.5 +/- 0.2 to 2.5 +/- 0.1 l . min-1 . m-2; SVR 17.4 to 14.6 torr/(l . min-1) although plasma histamine levels showed a comparable increase (1059 +/- 222 to 7653 +/- 4242 pg/ml). These data demonstrate directly that many of the hemodynamic effects of morphine can be attributed to histamine release. They further demonstrate that significant hemodynamic protection can be obtained by the use of histamine antagonists and the combination of H1 and H2 antagonists is superior to either given alone.

Blood Pressure↗
PubMed1986

The effects of combined H1 and H2 histamine antagonists on alterations in nasal airflow resistance induced by topical histamine provocation.

A clinical trial was undertaken to assess the effects of oral H1 (diphenhydramine hydrochloride) and H2 (cimetidine) histamine blockade on nasal resistance induced by topical histamine. Ten adult volunteers were tested on two separate occasions. Their noses were pretreated by oral administration of either combined H1 and H2 histamine antagonists or H1 antagonist and placebo. The nasal airflow resistive response to topical histamine was then determined. Combined histamine antagonism was significantly more effective in reducing the nasal resistive response to topical histamine than H1 antagonist alone (p less than 0.0001). Furthermore, ingestion of the oral H1 histamine antagonist, diphenhydramine hydrochloride, alone led to an increase in resistance of the unprovoked nose, whereas combined H1 and H2 antagonism did not lead to a significant change.

Adult↗
PubMed1996

Inverse agonism of histamine H2 antagonist accounts for upregulation of spontaneously active histamine H2 receptors.

Histamine H2 receptors transfected in Chinese hamster ovary (CHO) cells are time- and dose-dependently upregulated upon exposure to the H2 antagonists cimetidine and ranitidine. This effect appears to be H2 receptor-mediated as no change in receptor density was observed after H1 or H3 antagonist treatment or after incubation with the structural analogue of cimetidine, VUF 8299, which has no H2 antagonistic effects. By using transfected CHO cells expressing different densities of wild-type H2 receptors or an uncoupled H2Leu124Ala receptor, the histamine H2 receptor was found to display considerable agonist-independent H2 receptor activity. Cimetidine and ranitidine, which both induce H2 receptor upregulation, actually functioned as inverse agonists in those cell lines displaying spontaneous agonist-independent H2 receptor activity. Burimamide, on the other hand, was shown to act as a neutral antagonist and did as expected not induce H2 receptor upregulation after long-term exposure. The displayed inverse agonism of H2 antagonists appears to be a mechanistic basis for the observed H2 antagonist-induced H2 receptor upregulation in transfected CHO cells. These observations shed new light on the pharmacological classification of the H2 antagonists and may offer a plausible explanation for the observed development of tolerance after prolonged clinical use.

Animals↗
PubMed1985

Treatment with histamine H2 antagonists in acute upper gastrointestinal hemorrhage. Implications of randomized trials.

Histamine H2 antagonists are widely used in treating patients with hematemesis and melena, despite the lack of reliable evidence of benefit from any of the randomized trials, considered separately. Examination of the data from all 27 available randomized trials, in which over 2500 patients were entered, suggests that treatment may reduce the rates of rebleeding, surgery, and death by about 10, 20, and 30 per cent, respectively, although these results were only marginally significant for surgery and death. Any benefit appeared to be confined to patients with bleeding gastric ulcers, but since this subgroup analysis was prompted by preliminary examination of the data in some of the individual trials reviewed here, it should be treated with particular caution. The implications of this overview are that treatment with histamine H2 antagonists appears to be moderately promising, but its effects on important end points, such as death, still need to be assessed reliably. Prevention of "only" about 20 per cent of all deaths could well be worthwhile, for the condition is common, and the treatment widely practicable. To detect such a moderate effect reliably, however, might require the randomization of 10,000 patients (or more), which would be possible only in an extremely simple multicenter collaborative trial.

Acute Disease↗
PubMed1986

Histamine in dorsal and ventral hippocampus. II. Effects of H1 and H2 histamine antagonists on exploratory behavior in male rats.

The effects on Hole-Board behavior of histamine (HA) microinjected into different parts of the hippocampus and the effects of pyrilamine (PYR, an H1-histamine antagonist), ranitidine (RAN, an H2-histamine antagonist) or alpha-fluoromethyl-histidine (alpha-FMH, an irreversible inhibitor of the HA synthetizing enzyme) injected into the hippocampus on behavior were studied. Forty five nMol of HA were injected stereotaxically into the dorsal or ventral hippocampus. Five min later, Hole-board behavior was measured. It was observed that HA inhibited locomotion and rearing only in the rats injected into the ventral hippocampus. In other experiments, animals were microinjected into the ventral hippocampus with 135 nMol of PYR or RAN in 1 microliter of saline solution. Ten min later, they were microinjected with 45 nMol of HA. Hole-board exploratory activity was measured 5 min thereafter. Results showed that both PYR and RAN were effective in counteracting the inhibitory effect of HA on locomotor activity, but only RAN was able to block the inhibitory action of HA on rearing behavior. Head-dipping frequency was not affected by these treatments. In rats microinjected with 20 nMol of alpha-FMH, increased scores of locomotion were observed but the other behaviors (head-dipping frequency, grooming and rearing) were not affected. The present results support the hypothesis that HA in hippocampus may be exerting a regulatory role on behavior by interaction with H1 and H2 receptors.

Aminopyridines↗
PubMed1993

[Evaluation of the effect of H2-histamine antagonists in the natural history of stomach cancer].

On a study population of 131 patients the Authors evaluate possible differences related to the use of H2 blockers. Patients were divided in 2 groups: one (70 cases) studied before the introduction of H2 blockers and the other (61 cases) treated with H2 blockers. The influence of endoscopy for the early diagnosis of gastric cancer was also considered. The Authors conclude that H2 blockers do not have a negative influence from a surgical point of view, however the correct diagnosis may often be delayed and this is not acceptable for an era in which early diagnosis is feasible.

Female↗
PubMed1983

[H2 histamine antagonists and the hypothalamo-hypophyseal-gonadal axis: effect of short-term treatment on serum levels of prolactin, FSH, LH and testosterone in male ulcer patients].

Serum prolactin (PRL ng/ml) was measured in 7 male patients on cimetidine (CMT) and in 13 on ranitidine (RNT) before therapy and 5, 10, 15 and 30 days after; at the same intervals FSH (ng/ml), LH (ng/ml) and testosterone (ng/ml) were measured in 5 patients too, in order to ascertain hypothalamic, pituitary, gonadal dysfunction caused by H2 histamine blockers. In agreement with other authors, FSH, LH and testosterone were not affected: no statistical difference was found between basal values and the times of follow-up. In RNT-treated patients PRL showed a little, but not significant increase; in CMT-treated group PRL increased with a peak on 10th day (19.41 +/- 2.14 ng/ml vs. 9.50 +/- 1.72 ng/ml; P less than 0.01); on 30th day PRL levels were still higher than basal ones (15.85 +/- 2.38 ng/ml vs. 9.50 +/- 1.72 ng/ml; P less than 0.05). Unlike other trials we observed that PRL rises very early in oral treatment with CMT, perhaps for resetting of inhibiting factors, it trends to decrease and reach basal values shortly after 30th day notwithstanding therapy. It is now widely accepted that H2 blocker's action is on central histaminergic pathways modulating PRL secretion; in our opinion, the measured differences of PRL secretion with CMT and RNT in short term observations, are produced by different crossing of blood-brain barreer.

Adult↗
PubMed1987

Effects of toxic doses of a novel histamine (H2) antagonist on the rat thyroid gland.

The oral administration of high doses of a histamine H2 antagonist SK&F 93479 (up to 1000 mg/kg/day) to male rats for up to 21 days resulted in alterations in thyroid morphology indicative of increased activity of the thyroid gland. Measurement of thyroidal 125I incorporation substantiated these findings. Treatment with SK&F 93479 resulted in a dose-dependent increase in thyroidal iodide incorporation. This was apparent after a single dose of the compound and was reversible after dosing for 7 days. The increased incorporation of 125I into the thyroid gland was apparently dependent on thyroid-stimulating hormone (TSH) since both hypophysectomy and pretreatment with thyroxine (T4) markedly reduced thyroidal 125I uptake. Hypothalamic thyrotropin-releasing hormone (TRH) and pituitary TSH concentrations were not altered by SK&F 93479 treatment, and in TRH challenge experiments circulating TSH concentrations showed no change from control levels. These data suggest that hypothalamic-pituitary sensitivity was unaltered by treatment with SK&F 93479. Pharmacological ablation of thyroidal mast-cell function did not alter the thyroid response to 125I accumulation after SK&F 93479 dosing, indicating that the action of the compound is probably not dependent on changes in thyroid mast-cell histamine. Circulating T4 and TSH levels were altered in SK&F 93479-treated rats. Generally, T4 levels were reduced 6 hr after dosing and TSH levels were elevated 24 hr after dosing. Triiodothyronine (T3) levels were unaffected by SK&F 93479 treatment. The effect of SK&F 93479 treatment on T4 clearance was measured by examining the elimination of radioactivity from the circulation of rats previously injected with 125I-labelled T4. One oral dose of 1000 mg SK&F 93479/kg markedly increased T4 clearance. These results suggest that SK&F 93479 affects thyroid activity indirectly by a primary effect on T4 clearance. Reductions in circulating T4 lead to increased TSH levels and subsequent stimulation of thyroid activity.

Animals↗
PubMed1993

An evaluation of an anti-inflammatory-histamine H2 antagonist drug complex on gastric erosions in the rat.

The anti-inflammatory effect, gastrotoxicity and in vivo absorption property of the drug complex esterified flurbiprofen (FP) with histamine H2 antagonist, N-[3-(3-(1-piperidinylmethyl)phenoxy)propyl]-2- (2-hydroxyethylthio)acetamide (PPA), were compared with those of FP and FP methyl ester. The drug complex of FP with PPA (FP-PPA) was partly hydrolyzed in vitro in buffer (pH 1.2-7.4) in the presence or absence of pepsin and trypsin, slowly hydrolyzed in gastric mucosal homogenate and quickly hydrolyzed in 10% rat plasma (T1/2 = 35 sec). The hydrolysis rates of FP-PPA were the same as FP methyl ester in enzymatic and nonenzymatic medium. FP-PPA inhibited carrageenan-induced paw edema to the same extent as did FP alone. The plasma concentrations of FP after oral administration of FP derivatives were similar to FP alone. FP-PPA significantly reduced gastrotoxicity in comparison with an equivalent dose of FP, whereas the coadministration of FP and PPA did not affect the gastrotoxicity of FP. The gastrotoxicity of FP methyl ester was dependent on the drug concentration in gastric mucosa, whereas FP-PPA induced minor gastric erosion even at high mucosal drug complex concentration. These data suggested that FP-PPA, the drug complex of FP with histamine H2 antagonist, causes less gastric damage than ester prodrugs like methyl ester or free drug, FP.

Animals↗
PubMed1986

Protein binding properties of some histamine H2 antagonists: a 1H nuclear magnetic resonance study of antihistamine-calmodulin interactions.

Oxmetidine (SK & F 92994) is a potent histamine H2 antagonist, which, however, also demonstrates cardiac effects consistent with its inhibiting transmembrane calcium fluxes. 1H nuclear magnetic resonance has been used to show that oxmetidine binds to a single site on the regulatory calcium-binding protein, calmodulin. Binding requires the presence of at least two equivalents of calcium per mol protein, is characterized by fast exchange behaviour and a dissociation constant of about 4 mM and is not affected by the presence of trifluoperazine. Protein-induced spectral changes and a limited study of structure-affinity relationships suggest the importance of the drug imidazole and benzyldioxymethylene groups in determining the strength of the interaction. Drug-induced perturbations in the spectrum of calmodulin indicate that the binding site is in the C-terminal half of the protein, and involves a hydrophobic area containing His-107, Met-144, Met-145 and possibly Phe-89, Phe-141, and calcium binding site III.

Animals↗
PubMed1986

Inhibition of dimaprit- and pentagastrin-induced gastric acid secretion in cats by the new histamine H2 antagonist, CM 57755.

The antisecretory effects of CM 57755, a new histamine-H2 receptor antagonist, have been compared with those of cimetidine on gastric acid secretion induced by intravenous infusions of dimaprit or pentagastrin into conscious cats with chronically implanted gastric fistulae. Intravenous infusion of CM 57755 induced a parallel shift to the right of the dimaprit dose-response curve. The potency of CM 57755 was comparable with that of cimetidine as shown by similar doses causing a 5-fold displacement to the right of the dimaprit dose-response curve (4.9 mumol kg-1 h-1 for CM 57755 and 4.7 mumol kg-1 h-1 for cimetidine). Unlike that with dimaprit, the acid secretion stimulated by increasing doses of pentagastrin was inhibited by CM 57755 with depression of the maximal effect, indicating non-competitive antagonism. In a second series of experiments the time course of the anti-secretory action of intragastrically administered CM 57755 was studied from the gastric acid secretion induced by constant infusion of dimaprit. At equieffective doses, CM 57755 caused more sustained inhibition than cimetidine.

Animals↗
PubMed1992

Effect of a new non-steroidal anti-inflammatory combination of a histamine H2 antagonist and indomethacin on gastroduodenal mucosal membrane in rat.

The new non-steroidal anti-inflammatory drug (NSAID), N-(3-[3-(piperidinyl-methyl) phenoxy] propyl)-carbamoyl-methylthio]ethyl 1-(p-chlorobenzoyl) 5-methoxy-2-methyl-3-indolyl-acetate (CP 331, CAS 127966-70-5), a compound with a structure of an ester combining indomethacin (IM) and a histamine H2 antagonist, has been reported to have anti-inflammatory, analgesic and antipyretic effects. However, the influence of CP-331 on the gastroduodenal mucosa was not fully investigated. Therefore this study was undertaken to investigate the effect of CP-331 on the gastroduodenal mucosa membrane in rats. After single oral drug administration, the UD50 value (50% ulcerogenic dose) of CP-331 calculated from the incidence rate of gastric ulcer was higher than 1000 mg/kg; that for IM was 5.2 mg/kg. Moreover it was examined whether CP-331 had a preventive effect on NSAID-induced gastric damage. The results showed that the co-administration of CP-331 10-30 mg/kg prevented significantly the acute gastric mucosal injury caused by IM administration (20 mg/kg). CP-331 with anti-inflammatory activity does not cause gastric injury, moreover, because of its preventing and therapeutic effects on the damage to gastric mucous membrane induced by IM, CP-331 might be useful in the treatment of gastropathy caused by NSAID in clinic.

Animals↗
PubMed1977

[Treatment of peptic ulcer with histamine H2 receptor antagonists].

Histamine H2-receptor antagonists (Burimamide, Metiamide and Cimetidine as the most recent generation) may drastically inhibit gastric acid secretion stimulated by histamine, pentagastrin, insulin, 2-deoxyglucose or an intragastrically instilled meal, respectively. This inhibitory action may explain the beneficial effects of H2-antagonists in the treatment of active peptic ulceration. On Cimetidine administered at a usual dosage over a 4--6 week period, serious side-effects must not be expected. At present studies aim to establish a Cimetidine dosage which, on long-term treatment, may reduce ulcer recurrency.

Burimamide↗
PubMed1983

Effects of four H2 histamine antagonists on bethanechol-stimulated acid and pepsin secretion in the dog.

In five gastric fistula dogs, each of four H2-receptor antagonists was given (at doses roughly equal to the dose inhibiting histamine stimulation at 50%) as background infusion to graded doses of i.v. bethanechol. We measured acid and pepsin secretion and gastrin release. All four compounds noncompetitively inhibited acid secretion, reducing maximum acid outputs by 50 to 70%. Two compounds, tiotidine and cimetidine, shifted the bethanechol dose-response for pepsin secretion about 30% to the right at midpoint without reducing maximum output significantly, whereas the other two, ranitidine and metiamide, did not alter the dose-response. Dose-dependent gastrin release was unaffected by cimetidine, an imidazole compound, and augmented by tiotidine and ranitidine, the two nonimidazole compounds. Actions on pepsin and gastrin are thus not related to H2-receptor effects. The uniform effect of the four antagonists on acid secretion indicates an essential interaction between cholinergic and histamine effects on the parietal cell, although we could not distinguish between prereceptor, receptor and postreceptor sites for such interaction.

Animals↗