David Cavalla* and Richard Frith Pages 561 - 572 ( 12 )
The phosphodiesterases (PDEs) represent a group of enzymes controlling levels of intracellular cyclic AMP (cAMP). Because of the ubiquitous effects of this intracellular messenger, inhibitors of these enzymes have widespread effects. Phosphodiesterase IV represents one of the five main families of PDE with a presence in smooth muscle and inflammatory cells, selective inhibition of which been predicted to be of therapeutic advantage in asthma. There are 3 main classes of PDE IV inhibitor, relating to analogues of rolipram, nitraquazone, and xanthines. In vitro, PDE IV inhibitors are able to relax smooth muscle from the lung, and to reduce the production of inflammatory mediators from eosinophils, neutrophils, macrophages and lymphocytes. In vivo, these properties lead to bronchodilatation and inhibition of the late reaction and its sequelae that follow antigen challenge in sensitised animals. Clinical results to parallel these indicators of potential benefit in asthmatic patients have not yet been reported, but the panoply of potent and selective PDE IV inhibitors currently being progressed into the clinic will soon test this hypothesis.