Irsogladine: Overview of the Mechanisms of Mucosal Protective and Healing-Promoting Actions in the Gastrointestinal Tract

Irsogladine, a mucosal protective drug, was developed in Japan for the treatment of peptic ulcer disease and acute gastritis. This drug is superior to gefarnate, the same therapeutic category drug, in a randomized, controlled and double-blind clinical study in 1987. The mechanisms of irsogladine's actions are apparently different from those of antisecretory drugs. Irsogladine increases intracellular cyclic adenosine 3',5'-monophosphate content via non-selective inhibition of phosphodiesterase isozymes and exhibits gastric cytoprotection partly mediated by endogenous nitric oxide. These effects may account for a variety of actions of irsogladine in the gastrointestinal tract, including facilitation of gap junctional intercellular communication, inhibition of the reduced gastric mucosal blood flow response, suppression of reactive oxygen generation and so on. Since 1984, more than 60 papers have been published to further verify the effects of irsogladine on gap junctional intercellular communication, tight junction, nitric oxide production and neutrophil migration as well as Helicobacter pylori-related pathological changes in the stomach as well as the adverse reactions induced in the stomach or the small intestine by various drugs, including nonsteroidal anti-inflammatory drugs, bisphosphonates or selective serotonin re-uptake inhibitors. In this article, we review recent advances in understanding the mechanisms of irsogladine's actions and the most recent data in experimental as well as clinical studies.