New opioid receptor modulators and agonists

Alan D Kaye; Elyse M Cornett; Shilpa S Patil; Sonja A Gennuso; Matthew M Colontonio; Dustin R Latimer; Aaron J Kaye; Richard D Urman; Nalini Vadivelu

doi:10.1016/j.bpa.2018.06.009

New opioid receptor modulators and agonists

Best Pract Res Clin Anaesthesiol. 2018 Jun;32(2):125-136. doi: 10.1016/j.bpa.2018.06.009. Epub 2018 Jul 2.

Authors

Alan D Kaye¹, Elyse M Cornett², Shilpa S Patil³, Sonja A Gennuso⁴, Matthew M Colontonio⁵, Dustin R Latimer⁶, Aaron J Kaye⁷, Richard D Urman⁸, Nalini Vadivelu⁹

Affiliations

¹ Department of Anesthesiology, LSU Health Sciences Center, Room 656, 1542 Tulane Ave., New Orleans, LA, 70112, USA. Electronic address: akaye@lsuhsc.edu.
² Department of Anesthesiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA. Electronic address: ecorne@lsuhsc.edu.
³ Department of Anesthesiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA. Electronic address: spati1@lsuhsc.edu.
⁴ Department of Anesthesiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA. Electronic address: sgennu@lsuhsc.edu.
⁵ Department of Anesthesiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA. Electronic address: mcolo1@lsuhsc.edu.
⁶ Department of Anesthesiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA. Electronic address: dlatim@lsuhsc.edu.
⁷ Medical University of South Carolina, Charleston, SC, 29425, USA. Electronic address: aaronkaye44@yahoo.com.
⁸ Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School, Brigham and Women's Hospital, 75 Francis St, Boston, MA, 02115, USA. Electronic address: rurman@bwh.harvard.edu.
⁹ Department of Anesthesiology, Yale School of Medicine, 333 Cedar Street, TMP 3, PO Box 208051, New Haven, CT, 06520, USA. Electronic address: nalini.vadivelu@yale.edu.

PMID: 30322454
DOI: 10.1016/j.bpa.2018.06.009

Abstract

There has been significant research to develop an ideal synthetic opioid. Opioids with variable properties possessing efficacy and with reduced side effects have been synthesized when compared to previously used agents. An opioid modulator is a drug that can produce both agonistic and antagonistic effects by binding to different opioid receptors and therefore cannot be classified as one or the other alone. These compounds can differ in their structures while still possessing opioid-mediated actions. This review will discuss TRV130 receptor modulators and other novel opioid receptor modulators, including Mitragyna "Kratom," Ignavine, Salvinorin-A, DPI-289, UFP-505, LP1, SKF-10,047, Cebranopadol, Naltrexone-14-O-sulfate, and Naloxegol. In summary, the structural elucidation of opioid receptors, allosteric modulation of opioid receptors, new opioid modulators and agonists, the employment of optogenetics, optopharmacology, and next-generation sequencing of opioid receptor genes and related functionality should create exciting new avenues for research and therapeutic development to treat conditions including pain, opioid abuse, and addiction.

Keywords: TRV130; cebranopadol; ignavine; kratom; opioid crisis; opioid receptor modulators; opioid receptors.

Publication types

Review

MeSH terms

Analgesics, Opioid / metabolism*
Analgesics, Opioid / pharmacology*
Animals
Diterpenes, Clerodane / metabolism
Diterpenes, Clerodane / pharmacology
Humans
Indoles / metabolism
Indoles / pharmacology
Naltrexone / analogs & derivatives
Naltrexone / metabolism
Naltrexone / pharmacology
Receptors, Opioid / agonists*
Receptors, Opioid / metabolism*
Spiro Compounds / metabolism
Spiro Compounds / pharmacology
Thiophenes / metabolism
Thiophenes / pharmacology

Substances

((3-methoxythiophen-2-yl)methyl)((2-(9-(pyridin-2-yl)-6-oxaspiro(4.5)decan-9-yl)ethyl))amine
6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenylspiro(cyclohexane-1,1'(3'H)-pyrano(3,4-b)indol)-4-amine
Analgesics, Opioid
Diterpenes, Clerodane
Indoles
Receptors, Opioid
Spiro Compounds
Thiophenes
naltrexone-14-O-sulfate
Naltrexone
salvinorin A