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

Canine experiments were designed to determine if both histamine H1 and H2 receptors are present in the renal circulation. Renal blood flow (RBF) increased steeply over the first minute of intra-arterial histamine infusion, then increased gradually to a plateau in 3– –5 min. Infusion of either histamine + H2 antagonist or of H1 agonist produced the initial rapid increase in RBF, whereas infusion of either histamine + H1 antagonist or of H2 antagonist produced a slower but more sustained increase in RBF. Histamine significantly increased urine flow rate (V), chloride excretion, and glomerular filtration rate (GFR). Infusion of the H2 agonist also increased V and Cl excretion without affecting GFR. By contrast H1 agonist significantly reduced V and Cl excretion and tended to reduce GFR (P less than 0.1 greater than 0.05). Histamine, H1 agonist, and H2 agonist each increased inner cortical more than outer cortical blood flow. These data suggest that 1) H1 and H2 receptors are present in the renal vasculature, 2) changes in intrarenal blood flow distribution are not responsible for histamine-induced diuresis, and 3) H1 receptors are primarily postglomerular while H2 receptors exhibit both pre- and postglomerular distribution.

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

Food and Chemical Toxicology ◽

10.1016/0278-6915(87)90235-3 ◽

1987 ◽

Vol 25 (10) ◽

pp. 787-794 ◽

Cited By ~ 18

Author(s):

C.G. Brown ◽

R.F. Harland ◽

I.R. Major ◽

C.K. Atterwill

Keyword(s):

Thyroid Gland ◽

H2 Antagonist ◽

Histamine H2 Antagonist ◽

Rat Thyroid ◽

Rat Thyroid Gland

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Evaluation of target attainment of oral posaconazole suspension in immunocompromised children

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz481 ◽

2019 ◽

Vol 75 (3) ◽

pp. 726-729

Author(s):

Tony Lai ◽

Jan-Willem Alffenaar ◽

Alison Kesson ◽

Sushil Bandodkar ◽

Jason A Roberts

Keyword(s):

Retrospective Study ◽

Plasma Concentration ◽

Plasma Concentrations ◽

Invasive Fungal Disease ◽

Target Attainment ◽

Breakthrough Infection ◽

H2 Antagonist ◽

Starting Dose ◽

Histamine H2 Antagonist ◽

The Mean

Abstract Background Posaconazole is a broad-spectrum antifungal that is not licensed for use in children <13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease. Objectives To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children <13 years of age. Patients and methods We performed a retrospective study of immunocompromised children <13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded. Results A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3–980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P<0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70). Conclusions The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.

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Histamine receptor in bullfrog gastric mucosa

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1981.241.2.g93 ◽

1981 ◽

Vol 241 (2) ◽

pp. G93-G97

Author(s):

S. J. Hersey

Keyword(s):

Gastric Mucosa ◽

Histamine Receptor ◽

Histamine Receptors ◽

Histamine Antagonists ◽

Competitive Antagonism ◽

H2 Antagonist ◽

H2 Receptors ◽

High Concentrations ◽

H1 Antagonist ◽

Very High

The histamine receptor of isolated bullfrog gastric mucosa was characterized in terms of respiration and acid secretory responses to histamine antagonists and agonists. Cimetidine, a selective H2-antagonist, showed competitive antagonism of histamine responses with a pA2 value of 6.55. In contrast, the H1-antagonist, mepyramine, showed inhibition only at very high concentrations. Based on these results, the histamine receptor would be classified as the H2 type. Measurements of agonist potency sequence revealed a marked difference between the amphibian and mammalian gastric histamine receptors. The selective H1-agonists, 2-pyridylethylamine and 2-aminoethylthiozol, were found to be more efficacious than the selective H2-agonists, dimaprit and impromidine. The lack of efficacy for dimaprit and impromidine does not appear to be due to a lack of binding to the receptor because these agents inhibit responses to histamine. For dimaprit, the inhibition was found to be competitive with an apparent pA2 value of 5.37. These results indicate that there is a molecular difference between H2-receptors in mammals versus amphibians.

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Neuroimmune communication in the submucous plexus of guinea pig colon after sensitization to milk antigen

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.267.6.g1087 ◽

1994 ◽

Vol 267 (6) ◽

pp. G1087-G1093 ◽

Cited By ~ 13

Author(s):

T. Frieling ◽

H. J. Cooke ◽

J. D. Wood

Keyword(s):

Presynaptic Inhibition ◽

Neuronal Excitability ◽

Acetylcholine Release ◽

Submucous Plexus ◽

Mucosal Mast Cells ◽

H2 Antagonist ◽

Histamine H2 Antagonist ◽

Antigenic Exposure ◽

Beta Lactoglobulin ◽

Histamine H3

We investigated electrical and synaptic behavior of neurons in the colonic submucous plexus during exposure to beta-lactoglobulin in guinea pigs sensitized by ingestion of milk. Microelectrodes were used to record electrical and synaptic behavior in neurons from milk-sensitized and nonsensitized age-matched animals during exposure to beta-lactoglobulin. Neurons in sensitized animals were hyperexcitable. Application of the histamine H2 antagonist cimetidine reversed the hyperexcitability, suggesting endogenously released histamine as one of the responsible factors. Antigenic exposure suppressed stimulus-evoked nicotinic cholinergic fast excitatory postsynaptic potentials (EPSPs). This was blocked by the selective histamine H3 antagonist burimamide. Suppression of the EPSPs resulted from presynaptic inhibition of acetylcholine release. Increased neuronal excitability and suppression of synaptic transmission was only found in milk-sensitized intestine, not in the intestine from age-matched nonsensitized animals. We concluded that signaling from mucosal mast cells to the enteric nervous system is important in colonic defense against antigenic threats. Histamine is a paracrine messenger in the communication network.

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An Herbal H2 Blocker in Melasma Treatment

Current Drug Discovery Technologies ◽

10.2174/1570163816666190121145653 ◽

2020 ◽

Vol 17 (3) ◽

pp. 272-277

Author(s):

Marjan Mahjour ◽

Arash Khoushabi

Keyword(s):

Skin Pigmentation ◽

The Body ◽

Inflammatory Factor ◽

H2 Receptor ◽

Topical Drugs ◽

H2 Blockers ◽

H2 Blocker ◽

H2 Antagonist ◽

H2 Receptors ◽

Review Study

Background: Melasma is a skin pigmentation disorder that remains resistant to available therapies. The exact cause of melasma is unknown. Histamine is an inflammatory factor. Its involvement in pigmentation is obscure. The aim of this study is to introduce an herbal antihistamine H2 receptor which is effective in these disorders. Methods: This is a review study by searching the electronic databases and also Persian Medicine books, from 2000 to 2018 by the keywords such as H2 antagonist, H2 blocker and melasma. Results: According to the researched studies, histamine can induce melanogenesis and melasma after a series of stages in the body. Also, Histamine, through receptors 2, triggers melasma. Therefore, it can be said that antihistamine H2 receptor can be effective in melasma. Considering chemical antihistamine, H2 receptors have side effects, such as digestive problems, H2 antagonists can be used in the treatment of diseases such as dyspepsia but they have multiple complications. On the other hand, there is an herbal H2 antagonist that can be useful for melasma due to having some special properties. Conclusion: Herbal H2 blockers should be noted in melasma treatment along with the topical drugs.

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Suppression of pulmonary and systemic vascular histamine H2-receptors in allergic sheep

Journal of Applied Physiology ◽

10.1152/jappl.1986.60.3.791 ◽

1986 ◽

Vol 60 (3) ◽

pp. 791-797 ◽

Cited By ~ 6

Author(s):

T. Ahmed ◽

M. King

Keyword(s):

Vascular Resistance ◽

Histamine Receptor ◽

Base Line ◽

Group 14 ◽

H2 Antagonist ◽

H2 Receptors ◽

Pulmonary Arterial ◽

Histamine Response ◽

H1 Antagonist ◽

Vasodepressor Response

We have previously demonstrated a depression of airway H2-receptor function in sheep allergic to Ascaris suum antigen. To investigate whether this is a generalized defect, we studied the H1- and H2- histamine receptor functions in the pulmonary and systemic circulations of allergic and nonallergic sheep. Pulmonary arterial pressure, and cardiac output were measured for calculation of pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) before and immediately after a rapid intrapulmonary infusion of histamine (10 micrograms/kg), with and without pretreatment with H1- (chlorpheniramine) and H2- (metiamide) antagonists. Histamine alone increased mean PVR to 435 and 401% of base line and decreased mean SVR by 51 and 54% in the nonallergic and allergic sheep, respectively (P less than 0.001). In the nonallergic sheep following pretreatment with chlorpheniramine (selective H2 stimulation) or metiamide (selective H1 stimulation), histamine decreased SVR by 18 and 36%, respectively, suggesting that approximately two-thirds of the vasodepressor response was mediated by H1-receptors and one-third by H2-receptors. Combined H1- and H2-antagonists completely blocked the histamine response. In allergic sheep the histamine-induced decrease in SVR was primarily mediated by H1-receptors, because the response was blocked by H1-antagonist, chlorpheniramine, and the H2-antagonist, metiamide, had no effect. In the pulmonary circulation selective H1-stimulation caused a similar increase in PVR in allergic (365%) and nonallergic sheep (424%), whereas selective H2-stimulation caused a significant decrease in PVR in the nonallergic group (14%) but not in the allergic group.(ABSTRACT TRUNCATED AT 250 WORDS)

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