Unique Profile of Lafutidine, A Novel Histamine H2-Receptor Antagonist - Mucosal Protection Throughout Gastrointestinal Tract Mediated by Capsaicin-Sensitive Afferent Neurons -

Onodera, Sadayoshi; Nishida, K; Takeuchi, Koji

doi:10.2174/1567269043480681

Cited by 12 publications

(13 citation statements)

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“…Similar results have been obtained with another second-generation H 2 -receptor antagonist, roxatidine (Ichikawa et al, 1997(Ichikawa et al, , 1999. Lafutidine has been shown to enhance the healing of gastrointestinal mucosal lesions in a manner independent of its antacid secretory action (Kato et al, 2000;Onodera et al, 2004). However, lafutidine by itself does not have any direct effects on cell migration or proliferation.…”

Section: Mechanisms Of Gastroprotective Actionssupporting

confidence: 74%

Protective Effects of Gastric Mucus

Ichikawa¹,

Ishihara²

2011

Gastritis and Gastric Cancer - New Insights in Gastroprotection, Diagnosis and Treatments

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Section: Mechanisms Of Gastroprotective Actionssupporting

confidence: 74%

Protective Effects of Gastric Mucus

Ichikawa¹,

Ishihara²

2011

Gastritis and Gastric Cancer - New Insights in Gastroprotection, Diagnosis and Treatments

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“…We previously reported that lafutidine, a H 2 receptor antagonist, also protected against gastric lesions generated by the repeated administration of 5-FU [16]. This agent has been shown to have a potent antisecretory effect due to a blockade of histamine H 2 receptors and mucosal protective action in the gastrointestinal tract, including the esophagus, stomach, small intestine, and large intestine [11,12,14]. The latter effect is independent of the antisecretory action and is mediated by capsaicin-sensitive afferent neurons [11][12][13][14].…”

Section: Discussionmentioning

confidence: 99%

“…This agent has been shown to have a potent antisecretory effect due to a blockade of histamine H 2 receptors and mucosal protective action in the gastrointestinal tract, including the esophagus, stomach, small intestine, and large intestine [11,12,14]. The latter effect is independent of the antisecretory action and is mediated by capsaicin-sensitive afferent neurons [11][12][13][14]. Several studies also reported the important role of capsaicin-sensitive sensory neurons in the healing of gastric lesions [12,20,28].…”

Section: Discussionmentioning

confidence: 99%

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Impairment by 5-Fluorouracil of the Healing of Gastric Lesions in Rats: Effect of Lafutidine, a Histamine H2 Receptor Antagonist, Mediated by Capsaicin-Sensitive Afferent Neurons

et al. 2008

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We investigated the influence of 5-fluorouracil (5-FU), an anti-tumor agent, on the healing of gastric lesions generated by 0.6 M HCl in rats and the effect of lafutidine, a histamine H(2) receptor antagonist, on the impaired healing. Animals fasted for 18 h were given 1 ml of 0.6 M HCl p.o., fed normally from 1 h later, and killed 1-96 h thereafter. 5-FU was given i.v. twice, 1 h and 24 h after the HCl. The gastric lesions healed spontaneously within 96 h. Although it decreased acid secretion, 5-FU markedly delayed the healing. Lafutidine, but not cimetidine, given p.o. immediately after each dosing of 5-FU significantly reversed the delay in healing by 5-FU, and this effect was attenuated by the chemical ablation of capsaicin-sensitive afferent neurons. Capsaicin also significantly reversed the delay in healing. The mucosal application of 50 mM HCl did not affect gastric mucosal blood flow (GMBF) in the normal stomach, but significantly increased it in the stomach damaged by 0.6 M HCl. The increases in GMBF were attenuated by 5-FU; however, the co-administration of lafutidine significantly restored the response. In addition, 5-FU inhibited both cell proliferation and migration in rat gastric epithelial cells (RGM1) in vitro. These results suggest that 5-FU delayed the healing of gastric lesions generated by 0.6 M HCl, probably through the inhibition of cell migration and proliferation, as well as the impairment of GMBF, and lafutidine reversed the delay in healing, mainly through the amelioration of the GMBF response mediated by capsaicin-sensitive afferent neurons.

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“…The mucosal-protective effect of lafutidine is attenuated by pretreatment with the antagonist of CGRP (CGRP8-37) and the blocker of NO production (N G -nitro-L -arginine), as well as chemical ablation of capsaicin-sensitive sensory neurons, suggesting that this action appears through capsaicin-sensitive afferent neurons and is mediated by CGRP and NO [233] . Interestingly enough, lafutidine also exhibits a protective activity against the experimentally-induced mucosal lesions in digestive tissues other than the stomach, i.e.…”

Section: New H 2 -Receptor Antagonistsmentioning

confidence: 99%

Acid Suppression Therapy: Where Do We Go from Here?

Scarpignato

Pelosini²,

Mario³

2006

Dig Dis

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The dramatic success of pharmacological acid suppression in healing peptic ulcers and managing patients with gastroesophageal reflux disease (GERD) has been reflected in the virtual abolition of elective surgery for ulcer disease, a reduction in nonsteroidal anti-inflammatory drug (NSAID)-associated gastropathy and the decision by most patients with reflux symptoms to continue medical therapy rather than undergo surgical intervention. However, a number of challenges remain in the management of acid-related disorders. These include management of patients with gastroesophageal symptoms who do not respond adequately to proton pump inhibitor (PPI) therapy, treatment of patients with nonvariceal upper gastrointestinal bleeding, prevention of stress-related mucosal bleeding, optimal treatment and prevention of NSAID-related gastrointestinal injury, and optimal combination of antisecretory and antibiotic therapy for the eradication of Helicobacter pylori infection. A number of new drugs are currently being investigated to provide a significant advance on current treatments. Some of them (namely potassium-competitive acid blockers (P-CABs) and CCK₂-receptor antagonists) have already reached clinical testing while some others (like the antigastrin vaccine, H₃-receptor ligands or gastrin-releasing peptide receptor antagonists) are still in preclinical development and need the proof of concept in human beings. Of the current approaches to reduce acid secretion, P-CABs and CCK₂-receptor antagonists hold the greatest promise, with several compounds already in clinical trials. Although the quick onset of action of P-CABs (i.e. a full effect from the first dose) is appealing, the results of phase II studies with one such agent (namely AZD0865) did not show any advantages over esomeprazole. Thanks to their limited efficacy and the development of tolerance it is unlikely that CCK₂ antagonists will be used alone as antisecretory compounds but, rather, their combination with PPIs will be attempted with the aim of reducing the long-term consequences of hypergastrinemia. While H₂-receptor antagonists (especially soluble or over-the-counter formulations) will become the ‘antacids of the third millennium’ and will be particularly useful for on-demand symptom relief, clinicians will continue to rely on PPIs to control acid secretion in GERD and other acid-related diseases. In this connection, several new PPI formulations have been developed and two novel drugs (namely ilaprazole and tenatoprazole) are being studied in humans. The recently introduced immediate-release (IR) omeprazole formulation (currently available only in the USA) quickly increases intragastric pH and, given at bedtime, seems to achieve a better control of nocturnal acidity. IR formulations of other PPIs (including the investigational ones) will probably be available in the future and will enlarge our therapeutic armamentarium. Amongst the novel PPIs, tenatoprazole appears to be a true advance in the acid suppress...

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Unique Profile of Lafutidine, A Novel Histamine H2-Receptor Antagonist - Mucosal Protection Throughout Gastrointestinal Tract Mediated by Capsaicin-Sensitive Afferent Neurons -

Cited by 12 publications

References 0 publications

Protective Effects of Gastric Mucus

Protective Effects of Gastric Mucus

Impairment by 5-Fluorouracil of the Healing of Gastric Lesions in Rats: Effect of Lafutidine, a Histamine H2 Receptor Antagonist, Mediated by Capsaicin-Sensitive Afferent Neurons

Acid Suppression Therapy: Where Do We Go from Here?

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