Next Article in Journal
Enzymatic Responses to Low-Intensity Radiation of Tritium
Previous Article in Journal
Exposome and Immunity Training: How Pathogen Exposure Order Influences Innate Immune Cell Lineage Commitment and Function
Previous Article in Special Issue
Biphasic Force-Regulated Phosphorylation Site Exposure and Unligation of ERM Bound with PSGL-1: A Novel Insight into PSGL-1 Signaling via Steered Molecular Dynamics Simulations
Open AccessArticle

Novel Positive Allosteric Modulators of µ Opioid Receptor—Insight from In Silico and In Vivo Studies

1
Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory, Faculty of Pharmacy, 4A Chodźki St, PL-20093 Lublin, Poland
2
Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy, 4A Chodźki St, PL-20093 Lublin, Poland
3
School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70211 Kuopio, Finland
4
Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, AT-6020 Innsbruck, Austria
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8463; https://doi.org/10.3390/ijms21228463
Received: 19 August 2020 / Revised: 2 November 2020 / Accepted: 6 November 2020 / Published: 11 November 2020
(This article belongs to the Special Issue Computer Simulation on Membrane Receptors and Lipid Bilayers)
Opioids are the drugs of choice in severe pain management. Unfortunately, their use involves serious, potentially lethal side effects. Therefore, efforts in opioid drug design turn toward safer and more effective mechanisms, including allosteric modulation. In this study, molecular dynamics simulations in silico and ‘writhing’ tests in vivo were used to characterize potential allosteric mechanism of two previously reported compounds. The results suggest that investigated compounds bind to μ opioid receptor in an allosteric site, augmenting action of morphine at subeffective doses, and exerting antinociceptive effect alone at higher doses. Detailed analysis of in silico calculations suggests that first of the compounds behaves more like allosteric agonist, while the second compound acts mainly as a positive allosteric modulator. View Full-Text
Keywords: allosteric modulation; antinociceptive compounds; behavioral studies; molecular dynamics; opioid receptors allosteric modulation; antinociceptive compounds; behavioral studies; molecular dynamics; opioid receptors
Show Figures

Graphical abstract

MDPI and ACS Style

Bartuzi, D.; Kędzierska, E.; Kaczor, A.A.; Schmidhammer, H.; Matosiuk, D. Novel Positive Allosteric Modulators of µ Opioid Receptor—Insight from In Silico and In Vivo Studies. Int. J. Mol. Sci. 2020, 21, 8463. https://doi.org/10.3390/ijms21228463

AMA Style

Bartuzi D, Kędzierska E, Kaczor AA, Schmidhammer H, Matosiuk D. Novel Positive Allosteric Modulators of µ Opioid Receptor—Insight from In Silico and In Vivo Studies. International Journal of Molecular Sciences. 2020; 21(22):8463. https://doi.org/10.3390/ijms21228463

Chicago/Turabian Style

Bartuzi, Damian; Kędzierska, Ewa; Kaczor, Agnieszka A.; Schmidhammer, Helmut; Matosiuk, Dariusz. 2020. "Novel Positive Allosteric Modulators of µ Opioid Receptor—Insight from In Silico and In Vivo Studies" Int. J. Mol. Sci. 21, no. 22: 8463. https://doi.org/10.3390/ijms21228463

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop