Cargando…
New Avenues for Phosphodiesterase Inhibitors in Asthma
INTRODUCTION: Phosphodiesterases (PDEs) are isoenzymes ubiquitously expressed in the lungs where they catalyse cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (GMP), which are fundamental second messengers in asthma, thereby regulating the intracellular concentrations of the...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979323/ https://www.ncbi.nlm.nih.gov/pubmed/33758554 http://dx.doi.org/10.2147/JEP.S242961 |
_version_ | 1783667258707410944 |
---|---|
author | Matera, Maria Gabriella Ora, Josuel Cavalli, Francesco Rogliani, Paola Cazzola, Mario |
author_facet | Matera, Maria Gabriella Ora, Josuel Cavalli, Francesco Rogliani, Paola Cazzola, Mario |
author_sort | Matera, Maria Gabriella |
collection | PubMed |
description | INTRODUCTION: Phosphodiesterases (PDEs) are isoenzymes ubiquitously expressed in the lungs where they catalyse cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (GMP), which are fundamental second messengers in asthma, thereby regulating the intracellular concentrations of these cyclic nucleotides, their signaling pathways and, consequently, myriad biological responses. The superfamily of PDEs is composed of 11 families with a distinct substrate specificity, molecular structure and subcellular localization. Experimental studies indicate a possible role in asthma mainly for PDE3, PDE4, PDE5 and PDE7. Consequently, drugs that inhibit PDEs may offer novel therapeutic options for the treatment of this disease. AREAS COVERED: In this article, we describe the progress made in recent years regarding the possibility of using PDE inhibitors in the treatment of asthma. EXPERT OPINION: Many data indicate the potential benefits of PDE inhibitors as an add-on treatment especially in severe asthma due to their bronchodilator and/or anti-inflammatory activity, but no compound has yet reached the market as asthma treatment mainly because of their limited tolerability. Therefore, there is a growing interest in developing new PDE inhibitors with an improved safety profile. In particular, the research is focused on the development of drugs capable of interacting simultaneously with different PDEs, or to be administered by inhalation. CHF 6001 and RPL554 are the only molecules that currently are under clinical development but there are several new agents with interesting pharmacological profiles. It will be stimulating to assess the impact of such agents on individual treatable traits in specially designed studies. |
format | Online Article Text |
id | pubmed-7979323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-79793232021-03-22 New Avenues for Phosphodiesterase Inhibitors in Asthma Matera, Maria Gabriella Ora, Josuel Cavalli, Francesco Rogliani, Paola Cazzola, Mario J Exp Pharmacol Review INTRODUCTION: Phosphodiesterases (PDEs) are isoenzymes ubiquitously expressed in the lungs where they catalyse cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (GMP), which are fundamental second messengers in asthma, thereby regulating the intracellular concentrations of these cyclic nucleotides, their signaling pathways and, consequently, myriad biological responses. The superfamily of PDEs is composed of 11 families with a distinct substrate specificity, molecular structure and subcellular localization. Experimental studies indicate a possible role in asthma mainly for PDE3, PDE4, PDE5 and PDE7. Consequently, drugs that inhibit PDEs may offer novel therapeutic options for the treatment of this disease. AREAS COVERED: In this article, we describe the progress made in recent years regarding the possibility of using PDE inhibitors in the treatment of asthma. EXPERT OPINION: Many data indicate the potential benefits of PDE inhibitors as an add-on treatment especially in severe asthma due to their bronchodilator and/or anti-inflammatory activity, but no compound has yet reached the market as asthma treatment mainly because of their limited tolerability. Therefore, there is a growing interest in developing new PDE inhibitors with an improved safety profile. In particular, the research is focused on the development of drugs capable of interacting simultaneously with different PDEs, or to be administered by inhalation. CHF 6001 and RPL554 are the only molecules that currently are under clinical development but there are several new agents with interesting pharmacological profiles. It will be stimulating to assess the impact of such agents on individual treatable traits in specially designed studies. Dove 2021-03-15 /pmc/articles/PMC7979323/ /pubmed/33758554 http://dx.doi.org/10.2147/JEP.S242961 Text en © 2021 Matera et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Review Matera, Maria Gabriella Ora, Josuel Cavalli, Francesco Rogliani, Paola Cazzola, Mario New Avenues for Phosphodiesterase Inhibitors in Asthma |
title | New Avenues for Phosphodiesterase Inhibitors in Asthma |
title_full | New Avenues for Phosphodiesterase Inhibitors in Asthma |
title_fullStr | New Avenues for Phosphodiesterase Inhibitors in Asthma |
title_full_unstemmed | New Avenues for Phosphodiesterase Inhibitors in Asthma |
title_short | New Avenues for Phosphodiesterase Inhibitors in Asthma |
title_sort | new avenues for phosphodiesterase inhibitors in asthma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979323/ https://www.ncbi.nlm.nih.gov/pubmed/33758554 http://dx.doi.org/10.2147/JEP.S242961 |
work_keys_str_mv | AT materamariagabriella newavenuesforphosphodiesteraseinhibitorsinasthma AT orajosuel newavenuesforphosphodiesteraseinhibitorsinasthma AT cavallifrancesco newavenuesforphosphodiesteraseinhibitorsinasthma AT roglianipaola newavenuesforphosphodiesteraseinhibitorsinasthma AT cazzolamario newavenuesforphosphodiesteraseinhibitorsinasthma |