Download (4Mb) - Etheses - Saurashtra University

Part-1Review on Antiulcer Literaturebeen laid on the role of PPI’s in particular for the treatment of gastric acid disorders. Themedicinal chemistry aspects of this class of compounds are also discussed.Table 1: Some landmarks in therapy of acid-peptic disorders in past 35 years 2Year Company/Discoverer Event/Discovery1972 James Black et al 5 . Discovery of H 2 -receptor and H 2 -receptor antagonists1973 A. Ganser & J.Forte 6 Discovery of H + /K + -ATPase (The Proton Pump)1976 SmithKline & French 7 Cimetidine launched (H 2 -receptor antagonist)1982 Allen & Hanburys Ltd 8 Ranitidine launched (H 2 -receptor antagonist)1988 AstraZeneca 9 Omeprazole launched (PPI)1995 Takeda-Abbott 10 Lansoprazole launched (PPI)1997 Eisai Co.(licensed to Rabeprazole launched (PPI)Janssen) 112001 AstraZeneca 12 Esomeprazole launched (PPI)1.1.1 Mechanism of Gastric Acid SecretionStomach is a primary site of digestion. Presence of food stimulates release of acids andenzymes in stomach. The chemo- and mechanosensitive receptors present in stomach aretriggered by presence of food to produce specific responses. 2 The acid secreting parietalcell is the principle cell in gastric glands. The physiological regulation of acid secretionby the parietal cells is an important factor behind the rationale of use of various agents toreduce gastric acidity. Three major pathways activating parietal acid secretion includes;1) neuronal stimulation via the vagus nerve, 2) paracrine stimulation by local release ofhistamine from enterochromaffin-like (ECL) cells. 3) endocrine stimulation via gastrinreleased from antral G cells. In neuronal pathway, acetylcholine (Ach) released by vagalnerve directly stimulates gastric acid secretion through muscarinic M 3 receptors locatedon the basolateral membrane of parietal cells. The CNS is considered to be the chiefcontributor for initiating gastric acid secretion in response to the anticipation of food. Achindirectly stimulates release of histamine from enterchromaffine-like (ECL) cells in thefundus and gastrin from the G cells in the gastric antrum. ECL cells, the sole source pfgastric histamine involved in acid secretion, are present in close proximity to parietalcells. Histamine released from ECL cells activates parietal cells in paracrine fashion bybinding to H 2 receptors. Gastrin is primarily present in antral G cells. Release of gastrin is2