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PAN-selective inhibition of cAMP-phosphodiesterase 4 (PDE4) induces gastroparesis in mice.

Author: Abou SalehLina, AragonIleana V, BoydAbigail, KolotevaAnna, McDonoughWill, MurphyJames M, RichJustin, RichterWito

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Overview

This study found that pan-selective inhibition of PDE4, but not PDE3, causes gastric retention in mice, suggesting that this effect may underlie the nausea and vomiting commonly observed with PDE4 inhibitors in humans. The study also explored potential strategies to alleviate this side effect.
Paper Details　
Original Abstract of the Article :
Inhibitors of cAMP-phosphodiesterase 4 (PDE4) exert a number of promising therapeutic benefits, but adverse effects, in particular emesis and nausea, have curbed their clinical utility. Here, we show that PAN-selective inhibition of PDE4, but not inhibition of PDE3, causes a time- and dose-dependent...See full text at original site
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引用元：
https://pubmed.ncbi.nlm.nih.gov/32738081

データ提供：米国国立医学図書館（NLM）

PDE4 Inhibition: A Double-Edged Sword for Gastroparesis

Inhibitors of cAMP-phosphodiesterase 4 (PDE4) hold promise for treating various conditions, but adverse effects, including nausea and emesis, have hindered their clinical utility. This study investigates the impact of PAN-selective PDE4 inhibition on gastric emptying in mice. The researchers observed a time- and dose-dependent accumulation of food in the stomachs of mice, suggesting that PDE4 inhibition might impair gastric emptying, potentially contributing to nausea and emesis.

PDE4 Inhibition: A Potential Culprit for Gastroparesis

This study reveals a potential link between PDE4 inhibition and gastroparesis, a condition characterized by delayed gastric emptying and associated with nausea and vomiting. The researchers' findings highlight the importance of considering the potential gastrointestinal side effects of PDE4 inhibitors and carefully balancing therapeutic benefits with potential risks. Further research is needed to explore the mechanisms underlying PDE4 inhibition-induced gastroparesis and develop strategies to mitigate these adverse effects.

Gastroparesis: Understanding the Mechanisms and Mitigation

This study underscores the need for a thorough understanding of the mechanisms underlying gastroparesis and the potential role of PDE4 inhibition in its development. The researchers' findings emphasize the importance of careful patient selection and monitoring for potential side effects when using PDE4 inhibitors. Further research into alternative therapeutic strategies, including potential prokinetic agents, might be beneficial in mitigating the gastrointestinal side effects associated with PDE4 inhibition.

Dr.Camel's Conclusion

Just like a camel navigating a treacherous desert path, understanding the complex interplay between PDE4 inhibition and gastroparesis requires careful consideration. This study highlights the potential for PDE4 inhibition to contribute to gastroparesis, underscoring the need for careful patient selection, monitoring for side effects, and exploring alternative treatment strategies to optimize therapeutic benefits while minimizing adverse effects.

Date :
  1. Date Completed 2021-03-11
  2. Date Revised 2021-09-03
Further Info :

Pubmed ID

32738081

DOI: Digital Object Identifier

NIHMS1674101

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