TY - JOUR T1 - Which PPI? JF - Gut JO - Gut SP - 309 LP - 310 DO - 10.1136/gut.49.2.309 VL - 49 IS - 2 AU - M J S Langman Y1 - 2001/08/01 UR - http://gut.bmj.com/content/49/2/309.abstract N2 - The world of drug development is inevitably that of “me toos”. The successful new product is followed by its imitators. This became obvious when the first β blocking agent pronethalol was followed, from the same company, by the still widely used non-selective β blocker propranolol, and then by a range of other β blocking drugs with particular selectivities. These innovations were, broadly speaking, linked to improved targeting of receptors, hence leading to more precise pharmacodynamic profiling. The developments themselves were based on the prevailing state of the art knowledge of likely structural relationships between the designed molecule and the agonist whose actions were to be modulated. As that knowledge was imprecise, proof of potency depended on classical pharmacological studies in experimental animals or tissues.In the four decades which have since passed, our understanding of molecular structures and receptor binding have improved enormously. Molecular design is now driven by combinatorial chemistry and computer modelling,1 and the value of pharmacological studies more often lies in confirming compound activity rather than in determining its presence. Secondly, refinements of pharmacological understanding have allowed greater precision of agonist or antagonist functioning.In gastroenterology these decades have seen the sequential development of the histamine H2 receptor antagonists and the proton pump inhibitors (PPIs). It is therefore … ER -