Affinity of fentanyl and its derivatives for the σ1-receptor

Piotr F J Lipiński; Edina Szűcs; Małgorzata Jarończyk; Piotr Kosson; Sándor Benyhe; Aleksandra Misicka; Ján Cz Dobrowolski; Joanna Sadlej

doi:10.1039/c9md00222g

Affinity of fentanyl and its derivatives for the σ₁-receptor

Medchemcomm. 2019 Jun 13;10(7):1187-1191. doi: 10.1039/c9md00222g. eCollection 2019 Jul 1.

Authors

Piotr F J Lipiński¹, Edina Szűcs^{2

3}, Małgorzata Jarończyk⁴, Piotr Kosson⁵, Sándor Benyhe², Aleksandra Misicka^{1

6}, Ján Cz Dobrowolski⁴, Joanna Sadlej⁷

Affiliations

¹ Department of Neuropeptides , Mossakowski Medical Research Centre , Polish Academy of Sciences , 02-106 Warsaw , Poland . Email: plipinski@imdik.pan.pl.
² Institute of Biochemistry , Biological Research Centre , Hungarian Academy of Sciences , Szeged , Hungary.
³ Doctoral School of Theoretical Medicine , University of Szeged , Faculty of Medicine , Szeged , Hungary.
⁴ National Medicines Institute , 00-725 Warsaw , Poland.
⁵ Toxicology Research Laboratory , Mossakowski Medical Research Centre , Polish Academy of Sciences , 02-106 Warsaw , Poland.
⁶ Faculty of Chemistry , University of Warsaw , 02-093 Warsaw , Poland.
⁷ Faculty of Mathematics and Natural Sciences , Cardinal Stefan Wyszyński University in Warsaw , 1/3 Wóycickiego-Str. , 01-938 Warsaw , Poland.

Abstract

Fentanyl and its 11 commercially available derivatives were investigated as to their affinity for the σ₁ receptor. The parent compound is a rather poor binder (IC₅₀ = 4973 nM), but its close derivatives (benzylfentanyl or p-fluorofentanyl) have submicromolar affinities. Modelling provides a structural basis for the observed trends in activity.