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Neurosci Lett. 2018 Feb 18. pii: S0304-3940(18)30119-8. doi: 10.1016/j.neulet.2018.02.037. [Epub ahead of print]

Insights from molecular dynamics simulations to exploit new trends for the development of improved opioid drugs.

Author information

1
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1677, New York, NY 10029, United States. Electronic address: marta.filizola@mssm.edu.

Abstract

Having accidental deaths from opioid overdoses almost quadrupled over the past fifteen years, there is a strong need to develop new, non-addictive medications for chronic pain to stop one of the deadliest epidemics in American history. Given their potentially fewer on-target overdosing risks and other adverse effects compared to classical opioid drugs, attention has recently shifted to opioid allosteric modulators and G protein-biased opioid agonists as likely drug candidates to prevent and/or reverse opioid overdoses. Understanding how these molecules bind and activate their receptors at an atomistic level is key to developing them into effective new therapeutics, and molecular dynamics-based strategies are contributing tremendously to this understanding.

KEYWORDS:

Allosteric modulator; Biased agonism; Functional selectivity; Receptor; Structure

PMID:
29466721
PMCID:
PMC6098741
[Available on 2019-08-18]
DOI:
10.1016/j.neulet.2018.02.037

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