Updates in Drug Development Strategies against Peptic ulcer BB Subudhi 1* , SP Sahoo 2 and PK Sahu 1 1 School of pharmaceutical Science, Siksha O Anusandhan University, Bhubaneswar, Orissa, 751003, India 2 Research Center-II, Aurobindo Pharma Limited, Hyderabad, India 3 School of pharmaceutical Science, Siksha O Anusandhan University, Bhubaneswar, Orissa, 751003, India * Corresponding author: BB Subudhi, Associate Professor, Siksha O Anusandhan University School of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Ghatikia, Kalinganagar, Bhubaneswar, 751003, India, Tel: 919853945363; E-mail: bharatbhusans@gmail.com Rec date: Sep 16, 2015; Acc date: Feb 26, 2016; Pub date: Mar 4, 2016 Copyright: © 2016 Subudhi BB, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Traditional use of antacids and use of histamine inhibitors have become ineffective in the management of peptic ulcer. Irreversible inhibition of proton pump although reduces ulceration, in the long run leads to adverse issues. It has not been possible to develop an ideal proton pump inhibitor. In this scenario, search for alternatives by capitalizing on the multifactorial etiology of ulceration holds promise. Keywords: Peptic ulcer; Drug development; Terapeutic; Proton pump Introduction An ulcer occurring in the lower end of oesophagus, in the stomach usually along the less curvature and in duodenum is known as peptic ulcer or duodenal ulcer. It is associated with symptoms including epigastric gnawing, heart burn, acid eructations, nausea, vomiting, belching, bloating, anorexia, haemorrhage and anaemia. Peptic ulcer occurs due to an imbalance between mucosal damaging (acid, pepsin) and protecting (mucus, bicarbonate, Prostaglandin E2 and I2) mechanisms. Acid secretion is a physiologically important process of the stomach as gastric acid induces pepsinogen activation to initiate digestive process and kills bacteria and other microbes ensuring a stable intragastric environment [1]. Tere are three endogenous secretagogues called positive regulators of acid secretion. Tey are acetyl choline, histamine and gastrin [2-5]. Prostaglandins (PG E2 and I2) act as negative regulators of acid secretion. An imbalance in these regulators leads to peptic ulcer [6]. Another cause of Peptic ulcer is the Helicobacter pylori infection. Tis infection has no direct role but can induce the immune system which results in superfcial gastritis and when it becomes chronic it gradually results in peptic ulcer [7]. Te secretion of gastric acid occurs at the level of parietal cells of oxyntic glands in the gastric mucosa, producing 2-3 liters of gastric juice per day (HCl of pH 1). Based on the involvement of multiple factors in peptic ulcer [8], several therapeutic strategies have been adopted against it. Tese, include suppression of the aggressive factors with use of antacids, specifc antagonists of muscarinic -M1 receptors, gastrin receptors, histamine-H2 receptors, proton pump inhibitors (PPIs), mucoprotective agents, eradication of H. pylori and analogues of prostaglandins. Research for development of antiulcer agent, aims to address one or the other of these issues. Drugs Reducing Gastric Parietal Cell Stimulation in the Primary Level of Acid Secretion Process Terapeutic strategy for treating ulcer at the molecular level generally involves reducing acid secretion by inhibiting receptors/ mediators at the initial level, intermediate level and fnal level of acid secretion. In the initial level, the strategy aims to reduce secretion by preventing stimulation to transmitters including histamine, acetylcholine and gastrin. Te intermediate level mainly involves interference on the role of carbonic anhydrase in promoting acid secretion. In the fnal stage it is the proton pump (H+ K+ ATPase) which has been the target for inhibition to reduce acid secretion. Acetylcholine inhibitors: Pfeifer [9] suggested that secretion of acid, mucus and pepsinogen in the gastric mucosal is stimulated via muscarinic receptors. Over expression of M3 receptors in duodenal ulcer patients is proved by autoradiographic techniques; thus blockade of this receptor subtype will reduce the pain by decreasing the duodenal motility and provide an efective anti-secretory therapy. Based on the high afnity to block the muscarinic receptors on the intramural ganglia of stomach wall, pirenzepine was developed as an anti-secretory drug, which was followed by telenzepine, a more potent derivative with improved healing rates [10]. Parasympathetic side efects [11] of these agents include dry mouth, blurred vision and constipation. Tese side efects along with their incomplete inhibition of gastric acid secretion limit their clinical utility. Histamine inhibitors: H2 receptor antagonists competitively inhibit the interaction of histamine with H2 receptors, thereby reducing both volume and H+ ion concentration of the gastric juice. Tey are selective and have little or no efect on H1 receptors. Tey also inhibit acid secretion elicited by gastrin, muscarinic agonists, food, sham feeding, fundic distension, as well as, other pharmacological agents. Tey also inhibit basal and nocturnal acid secretion. Tis efect contributes in a major way to their clinical efcacy. Black et al. [12] identifed H2-receptor and prototype H2-receptor antagonist, burimamide. Te potency of burimamide at inhibiting gastric acids secretion far exceeded than that produced by anticholinergic drugs and was devoid of side efects. However, it had poor bioavailability which was subsequently replaced by metiamide [13] which also because of its Subudhi et al., J Gastrointest Dig Syst 2016, 6:2 DOI: 10.4172/2161-069X.1000398 Review Article Open Access J Gastrointest Dig Syst ISSN:2161-069X JGDS, an open access journal Volume 6 • Issue 2 • 1000398 J o u r n a l o f G a s t r o i n t e s t i n a l & D i g e s t i v e S y s t e m ISSN: 2161-069X Journal of Gastrointestinal & Digestive System