Binding preference at the μ-opioid receptor underlies distinct pharmacology of cyclopropyl versus valeryl analogs of fentanyl.

ABSTRACT: Illicitly manufactured fentanyl is driving the current opioid crisis, and various fentanyl analogs are appearing in recreational drug markets worldwide. To assess the potential health risks posed by fentanyl analogs, it is necessary to understand structure-activity relationships for these compounds. Here we compared the pharmacology of two structurally related fentanyl analogs implicated in opioid overdose: cyclopropylfentanyl and valerylfentanyl. Cyclopropylfentanyl has a three-carbon ring attached to the carbonyl group on the fentanyl scaffold, whereas valerylfentanyl has a four-carbon chain at the same position. In vitro assays examining μ-opioid receptor (MOR) coupling to G proteins in CHO cells showed that cyclopropylfentanyl is a full agonist (EC₅₀ = 8.6 nM, %Emax = 113%),

SUBMITTER: Xie B 

PROVIDER: S-EPMC9974845 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature