Phosphodiesterase 4 inhibitors for the treatment of COPD.
Phosphodiesterase 4 (PDE4) is a major cyclic adenosine-3',5'-monophosphate-metabolizing enzyme in immune and inflammatory cells, airway smooth muscle, and pulmonary nerves. Selective inhibitors of this enzyme have been available for a number of years and show a broad spectrum of activity in animal models of COPD and asthma. The class-associated side effects, mainly nausea and emesis, appear to have been at least partially overcome by the so-called "second-generation" PDE4 inhibitors. Currently, three companies are in the later stages of development of candidate second-generation PDE4 inhibitors for the treatment of COPD patients. The preclinical profile of one of these, BAY 19-8004, is summarized below. The initial clinical data on the most advanced compound, cilomilast, were indeed encouraging. However, full knowledge of the therapeutic value of this novel compound class awaits the outcome of longer term clinical trials.
Sturton
Graham
G
Bayer plc, Pharma Research, Stoke Court, Stoke Poges, Slough SL2 4LY, Berkshire, UK. graham.sturton.gs@bayer.co.uk
Fitzgerald
Mary
M
D000631:Aminopyridines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002264:Carboxylic Acids; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003509:Cyclohexanecarboxylic Acids; D003521:Cyclopropanes; D006801:Humans; D009570:Nitriles; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
D000631:Aminopyridines; D001549:Benzamides; D001993:Bronchodilator Agents; D002264:Carboxylic Acids; D003509:Cyclohexanecarboxylic Acids; D003521:Cyclopropanes; D009570:Nitriles; D010726:Phosphodiesterase Inhibitors; C424423:Roflumilast; C433247:Cilomilast