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

P. S. Portoghese; M. Sultana; H. Nagase; A. E. Takemori

doi:10.1016/0014-2999(92)90167-3

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

P. S. Portoghese
, M. Sultana
, H. Nagase
, A. E. Takemori

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

191 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	195-196
Number of pages	2
Journal	European Journal of Pharmacology
Volume	218
Issue number	1
DOIs	https://doi.org/10.1016/0014-2999(92)90167-3
State	Published - Jul 21 1992

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SDG 3 Good Health and Well-being

Keywords

7-Benzylidenenaltrexone (BNTX)
Antinociception
δ-Opioid receptor subtypes binding

Publisher link

10.1016/0014-2999(92)90167-3

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title = "A highly selective δ1-opioid receptor antagonist: 7-benzylidenenaltrexone",

abstract = "In guinea pig brain membranes 7-benzylideneraltrexone (BNTX) possesses 100-fold greater affinity (Ki = 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.",

keywords = "7-Benzylidenenaltrexone (BNTX), Antinociception, δ-Opioid receptor subtypes binding",

author = "Portoghese, \{P. S.\} and M. Sultana and H. Nagase and Takemori, \{A. E.\}",

year = "1992",

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T1 - A highly selective δ1-opioid receptor antagonist

T2 - 7-benzylidenenaltrexone

AU - Portoghese, P. S.

AU - Sultana, M.

AU - Nagase, H.

AU - Takemori, A. E.

PY - 1992/7/21

Y1 - 1992/7/21

N2 - In guinea pig brain membranes 7-benzylideneraltrexone (BNTX) possesses 100-fold greater affinity (Ki = 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.

AB - In guinea pig brain membranes 7-benzylideneraltrexone (BNTX) possesses 100-fold greater affinity (Ki = 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.

KW - 7-Benzylidenenaltrexone (BNTX)

KW - Antinociception

KW - δ-Opioid receptor subtypes binding

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