Ramiper Mechanism of Action

Pharmacology: Preventive or healing effects in gastric ulcer models: Rebamipide inhibited gastric mucosal injury of ulcers, including ulcers induced by water-immersion restraint stress, acetylsalicylic acid, indomethacin, histamine, serotonin, and pyloric ligation. Rebamipide also protected the mucosa from injury caused by other ulcerogenic condition. Rebamipide promoted healing of gastric ulcers and suppressed recurrence or relapse of ulcers even 120-140 days after ulcer induction production.
Preventive or healing effects in gastritis models: Rebamipide inhibited the occurrence of taurocholic acid induced gastritis and promoted healing of mucosal inflammation.
Prostaglandin-increasing effect: Rebamipide increased the endogenous prostaglandin E₂ (PGE₂) in the gastric mucosa. Rebamipide also increased the PGE₂ and PGI₂, as well as 15-keto-13,4-dihydro-PGE₂ (a metabolite of PGE₂) and PGI₂ in the gastric juice. Rebamipide revealed the effect of increasing the PGE₂ content in the gastric mucosa and protected the gastric mucosa from injury caused by ethanol loading.
Cytoprotective effect: Rebamipide exhibited a gastric cytoprotective effect to inhibit mucosal injury induced by ethanol, strong acid, and strong base.
Mucus-increasing effect: Rebamipide promoted gastric enzyme activity to synthesize high molecular weight glycoproteins, thickened the superficial mucous layer of gastric mucosa, and increased the amount of gastric surface mucus and soluble mucus. Endogenous PGs were not involved in the increase in soluble mucus.
Mucosal blood flow-increasing effect: Rebamipide increased gastric mucosal blood flow and improved impaired hemodynamics after blood loss.
Effect on mucosal barrier: Rebamipide did not ordinarily affect the gastric transmucosal potential difference, but did inhibit lowering of the potential difference by ethanol.
Effect on gastric alkaline secretion: Rebamipide promoted gastric alkaline secretion.
Effect on mucosal cell turnover: Rebamipide activated gastric mucosal cell proliferation and increased the number of gastric epithelial cells.
Effect on gastric mucosal repair: Rebamipide restored the bile acid- or hydrogen peroxide-induced retardation of artificial wound-repair in gastric epithelial cells.
Effect on gastric secretion: Rebamipide did not alter either basal secretion of gastric juice or secretagogue-stimulated acid secretion.
Effect on oxygen-free radicals: Rebamipide scavenged hydroxyl radicals directly and suppressed superoxide production by polymorphonuclear leukocytes. Rebamipide also protected the gastric mucosal cells against injury caused by oxygen-free radicals released. Rebamipide inhibited mucosal injury and reduced the content of lipid peroxide in the gastric mucosa treated with indomethacin under stressed conditions.
Effect on inflammatory cellular infiltration in the gastric mucosa: Rebamipide prevented inflammatory cellular infiltration of taurocholic acid-induced gastritis, NSAID-induced gastric mucosal damage, and ischemia-perfusion-induced gastric mucosal damage.
Effects on inflammatory cytokine released (interleukin-8) in the gastric mucosa: Rebamipide suppressed the increased production and released of interleukin-8 from human gastric mucosa. Rebamipide also inhibited the activation of NF-kB and suppressed the expression of interleukin-8 mRNA in epithelial cells.