JUL 03, 2019 6:36 AM PDT

Common Anticonvulsant Drug May Counteract Inflammation

WRITTEN BY: Nouran Amin

Sepsis is a serious medical condition that results from inflammation in the body and can cause fatal multi-organ dysfunction. The inflammation is usually triggered from a chromosomal protein called high-mobility group box 1 (HMGB1) that is secreted from immune or dying cells. Current treatments methods to counteract the inflammation lacks efficacy however, a common anticonvulsant and vasodilating drug called papaverine, discovered recently by scientists through a computer software-based docking study, may provide a strong therapeutic method.

Learn more about sepsis:

"Our research group has been trying to identify compounds, preferably based on existing drugs, that block the binding of irritants to cellular receptors,” says senior researcher, Professor Sei-ichi Tanuma from Tokyo University of Science (TUS). “We want to find novel drugs to treat inflammation-based conditions.”

Supposedly, papeverine can effectively counteract the inflammation in septic conditions by inhibiting the binding of HMGB1 to its receptor—known as RAGE. Findings of the study published in Biochemical and Biophysical Research Communications describes a novel approach involving the utilization of a computer software program known as "COSMOS” to develop a small protein that mimics the RAGE-binding domain of HMGB1. Results indicated that the designed protein effectively mimicked the binding domain and "competitively inhibited" the HMGB1-RAGE interaction. Using data generated from the DrugBank Library, they concluded that papaverine was structurally similar to the protein they designed.

"This in silico drug design approach, to find novel effects of papaverine, is a unique strategy employed for the first time only by TUS researchers,” says Professor Tanuma.

Laboratory studies have shown that papaverine successfully reduced death rates among model mice.

"Drug repositioning using the in silico drug discovery approach used in our research can repurpose existing drugs into novel therapeutic agents. Also, because the cost of 'designing' a novel drug is saved, such approaches can also radically reduce the cost of medical treatment. The next step is to understand the degree to which papaverine blocks HMGB1-RAGE interaction in the human body. We are now trying to optimize the structure of papaverine to design a more 'effective' drug for the future."

Source: Science Daily

About the Author
BS/MS
Nouran is a scientist, educator, and life-long learner with a passion for making science more communicable. When not busy in the lab isolating blood macrophages, she enjoys writing on various STEM topics.
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