Fentanyl but not Morphine Interacts with Nonopioid Recombinant Human Neurotransmitter Receptors and Transporters

The Journal of Pharmacology and Experimental Therapeutics
Randy TorralvaAaron Janowsky

Abstract

Synthetic opioids, including fentanyl and its analogs, have therapeutic efficacy in analgesia and anesthesia. However, their illicit use in the United States has increased and contributed to the number one cause of death for adults 18-50 years old. Fentanyl and the heroin metabolite morphine induce respiratory depression that can be treated with the μ opioid receptor (MOR) antagonist naloxone. With higher or more rapid dosing, fentanyl, more than morphine, causes chest wall rigidity and can also induce rapid onset laryngospasm. Because non-MORs could mediate differing clinical manifestations, we examined the interactions of fentanyl and morphine at recombinant human neurotransmitter transporters, G protein-coupled receptors, and the N-methyl-D-aspartate glutamate receptor. Both drugs were agonists at MOR, κ, and δ opioid receptors. Morphine had little or no affinity at other human receptors and transporters (Ki or IC50 value >100 µM). However, fentanyl had Ki values of 1407 and 1100 nM at α1A and α1B adrenoceptor subtypes, respectively, and Ki values of 1049 and 1670 nM at dopamine D4.4 and D1 receptor subtypes, respectively; it also blocked [3H]neurotransmitter uptake by the vesicular monoamine transporter 2 (IC50 = 911 nM). P...Continue Reading

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Citations

Jun 24, 2021·Physiology·Ralph Lydic, Helen A Baghdoyan
May 25, 2021·British Journal of Pharmacology·Eamonn KellyGraeme Henderson
Sep 2, 2021·Journal of Neurophysiology·Christopher B O'BrienRalph Lydic

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