A highly selective δ₁-opioid receptor antagonist: 7-benzylidenenaltrexone

In guinea pig brain membranes 7-benzylideneraltrexone (BNTX) possesses 100-fold greater affinity (K_i = 0.1 nM) for [³H]DPDPE [³H][D-Pen²,D-Pen⁵]enkephalin) binding sites (δin1) relative to those of [³H]DSLET ([³H][D-Ser², Leu⁵] enkephalin-Thr⁶) (δ₂). The ED₅₀ dose ratio (tail flick) in mice for the antagonism of DPDPE-induced antinociception of BNTX (6.3 pmol i.c.v.) was 7.2, whereas for DSLET, morphine and U69593 it was not significantly different from unity. The fact that there was no correlation of the binding or in vivo data for BNTX with antagonist potency in smooth muscle preparations suggest that the in vitro pharmacologic activity is mediated by δ-opioid subtypes that are different from those in the brain.