Paper Details

  1. Home
  2. Paper Details

Identification of Major Esterase Involved in Hydrolysis of Soft Anticholinergic (2R3'R-SGM) Designed From Glycopyrrolate in Human and Rat Tissues.

Author: BodorNicholas, ImaiTeruko, OhuraKayoko, SamirAhmed

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Overview

2R3'R-SGM, a glycopyrrolate soft analog, is easily hydrolyzed into the less active zwitterionic metabolite, SGa. This study investigated the hydrolysis of 2R3'R-SGM in human and rat tissues. In both species, 2R3'R-SGM was metabolized to 2R3'R-SGa in plasma but was stable in liver and intestine. The half-life of 2R3'R-SGM was 16.9 min in human plasma and 9.8 min in rat plasma. The hydrolysis was mediated by plasma paraoxonase 1 (PON1), which is naturally attached to high-density lipoprotein and might be absent in topical tissues. This indicates that 2R3'R-SGM is an ideal soft drug that is detoxified rapidly in systemic circulation, while maintaining local stability and efficacy.
Paper Details　
Original Abstract of the Article :
The glycopyrrolate soft analog, SGM, designed to be easily hydrolyzed into the significantly less active zwitterionic metabolite, SGa, typifies soft drug that reduces systemic side effects (a problem often seen with traditional anticholinergics) following local administration. In this study, hydroly...See full text at original site
Dr.Camel IconDr.Camel's Paper Summary Blogラクダ博士について

ラクダ博士は、Health Journal が論文の内容を分かりやすく解説するために作成した架空のキャラクターです。
難解な医学論文を、専門知識のない方にも理解しやすいように、噛み砕いて説明することを目指しています。

* ラクダ博士による解説は、あくまで論文の要点をまとめたものであり、原論文の完全な代替となるものではありません。詳細な内容については、必ず原論文をご参照ください。
* ラクダ博士は架空のキャラクターであり、実際の医学研究者や医療従事者とは一切関係がありません。
* 解説の内容は Health Journal が独自に解釈・作成したものであり、原論文の著者または出版社の見解を反映するものではありません。


引用元：
https://doi.org/10.1016/j.xphs.2019.03.030

データ提供：米国国立医学図書館（NLM）

Investigating the Hydrolysis of SGM, a Soft Anticholinergic

The world of pharmaceuticals is a vast desert, filled with intricate pathways and complex interactions. This study explores the metabolism of SGM, a novel anticholinergic designed to be easily hydrolyzed into a less active form, reducing systemic side effects. The researchers investigated the breakdown of SGM in human and rat tissues, identifying plasma paraoxonase 1 (PON1) as the key enzyme responsible for its hydrolysis. This finding has significant implications for the development of targeted and safer drug delivery systems.

SGM: A Soft Drug with a Unique Metabolic Profile

The study found that SGM, a soft anticholinergic, is rapidly metabolized by PON1 in plasma, reducing its systemic side effects. This targeted breakdown ensures localized efficacy while minimizing unwanted systemic effects. The researchers also confirmed that SGM is stable in liver and intestine, suggesting a potentially safer drug delivery system. This innovative approach to drug design could pave the way for more targeted and effective treatments.

Harnessing the Power of Soft Drugs: A New Frontier in Pharmacology

The concept of soft drugs, like SGM, offers a promising approach to drug development, aiming to minimize systemic side effects and maximize localized efficacy. The study's findings suggest that SGM's unique metabolic profile could be leveraged for the development of safer and more effective anticholinergic treatments, leading to improved patient outcomes. This innovative approach to drug design has the potential to revolutionize how we develop and administer medications.

Dr. Camel's Conclusion

The study's findings demonstrate the potential of soft drugs, like SGM, to revolutionize the way we treat various medical conditions. The targeted breakdown of SGM, mediated by PON1, offers a promising strategy for minimizing systemic side effects and maximizing localized efficacy. This research opens a new chapter in drug development, offering exciting possibilities for safer and more effective therapies.

Date :
  1. Date Completed 2020-08-17
  2. Date Revised 2020-08-17
Further Info :

Pubmed ID

30954525

DOI: Digital Object Identifier

10.1016/j.xphs.2019.03.030

Related Literature

Article Analysis
・Side Effects of glycopyrronium topical
SNS
PICO Info
in preparation
Languages

English

Positive IndicatorAn AI analysis index that serves as a benchmark for how positive the results of the study are. Note that it is a benchmark and requires careful interpretation and consideration of different perspectives.

This site uses cookies. Visit our privacy policy page or click the link in any footer for more information and to change your preferences.