PDE inhibitors currently in early clinical trials for the treatment of asthma

Expert Opin Investig Drugs. 2014 Sep;23(9):1267-75. doi: 10.1517/13543784.2014.921157. Epub 2014 May 28.

Abstract

Introduction: PDE inhibitors could be useful in the treatment of asthma because of their bronchodilator and/or anti-inflammatory activities. Recently, some selective PDE3, PDE4 and PDE3/4 inhibitors have been shown to have beneficial effects in patients with asthma suggesting that such drugs may offer novel therapeutic options for the treatment of this disease.

Areas covered: The authors describe the main PDE families that could be involved in asthma as well as the PDE inhibitors that have been evaluated for the treatment of asthma.

Expert opinion: Although the potential therapeutic utility of PDE inhibitors has been demonstrated in various animal models of asthma, their clinical efficacy have been restricted by the dose-limiting side effects; no PDE inhibitor has yet been approved for the treatment of patients with asthma. Although new PDE inhibitors have been synthesised, most data are from cellular and tissue-level studies with human trials still on the horizon. Apparently, only CHF 6001, an inhaled PDE4 inhibitor, and RPL554, a dual PDE3/4 inhibitor, are still under clinical development. Further data from these new drugs are eagerly anticipated to better understand where these drugs might stand in the future treatment of asthma.

Keywords: PDE inhibitors; PDE isoforms; RPL554; asthma.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / pharmacology
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / pharmacology
  • Bronchodilator Agents / therapeutic use
  • Clinical Trials as Topic
  • Drug Design
  • Humans
  • Phosphodiesterase 3 Inhibitors / adverse effects
  • Phosphodiesterase 3 Inhibitors / therapeutic use*
  • Phosphodiesterase 4 Inhibitors / adverse effects
  • Phosphodiesterase 4 Inhibitors / therapeutic use*

Substances

  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Phosphodiesterase 3 Inhibitors
  • Phosphodiesterase 4 Inhibitors