Experimental and investigational phosphodiesterase inhibitors in development for asthma

Expert Opin Investig Drugs. 2019 Mar;28(3):261-266. doi: 10.1080/13543784.2019.1571582. Epub 2019 Jan 24.

Abstract

Introduction: Severe, inadequately-controlled asthma remains a clinical challenge. For this reason, clinical trials and preclinical experimental studies on novel agents as an add-on therapies continue emerge. Phosphodiesterases (PDEs) are enzymes that regulate the function of immune cells by hydrolyzing cyclic guanosine monophosphate/cGMP and cyclic adenosine monophosphate/cAMP. PDEs are divided into subfamilies [PDE3, PDE4, PDE5 and PDE7] which are mainly found in the respiratory tract. Inhibitors of PDEs have already been approved for COPD and pulmonary hypertension.

Areas covered: The role of PDE inhibitors in asthma treatment and the possible mechanism of action via their anti-inflammatory and/or bronchodilating effect are discussed.

Expert opinion: Novel PDE inhibitors exhibiting fewer adverse events may have a role as add-on therapies in asthma treatment in the future. More clinical trials are necessary to prove their efficacy and evaluate their safety profile before approval by regulatory bodies is granted.

Keywords: Asthma; PDE inhibitors; neutrophilic asthma; novel agents.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / pharmacology*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Drug Development / methods
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacology
  • Humans
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / adverse effects
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / drug effects
  • Phosphoric Diester Hydrolases / metabolism

Substances

  • Anti-Asthmatic Agents
  • Drugs, Investigational
  • Phosphodiesterase Inhibitors
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • Cyclic GMP