Emerging insights into mu opioid pharmacology

21Citations
Citations of this article
20Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Opioid analgesics, most of which act through mu opioid receptors, have long represented valuable therapeutic agents to treat severe pain. Concerted drug development efforts for over a 100 years have resulted in a large variety of opioid analgesics used in the clinic, but all of them continue to exhibit the side effects, especially respiratory depression, that have long plagued the use of morphine. The recent explosion in fatalities resulting from overdose of prescription and synthetic opioids has dramatically increased the need for safer analgesics, but recent developments in mu receptor research have provided new strategies to develop such drugs. This chapter reviews recent advances in developing novel opioid analgesics from an understanding of mu receptor structure and function. This includes a summary of the mechanism of agonist binding deduced from the crystal structure of mu receptors. It will also highlight the development of novel agonist mechanisms, including biased agonists, bivalent ligands, and allosteric modulators of mu receptor function, and describe how receptor phosphorylation modulates these pathways. Finally, it will summarize research on the alternative pre-mRNA splicing mechanisms that produces a multiplicity of mu receptor isoforms. Many of these isoforms exhibit different pharmacological specificities and brain circuitry localization, thus providing an opportunity to develop novel drugs with increased therapeutic windows.

Cite

CITATION STYLE

APA

Pasternak, G. W., Childers, S. R., & Pan, Y. X. (2020). Emerging insights into mu opioid pharmacology. In Handbook of Experimental Pharmacology (Vol. 258, pp. 89–125). Springer. https://doi.org/10.1007/164_2019_270

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free