Favourable involvement of α 2A-adrenoreceptor antagonism in the I 2-imidazoline binding sites-mediated morphine analgesia enhancement

Valerio Mammoli; Alessandro Bonifazi; Fabio Del Bello; Eleonora Diamanti; Mario Giannella; Alan L. Hudson; Laura Mattioli; Marina Perfumi; Alessandro Piergentili; Wilma Quaglia; Federica Titomanlio; Maria Pigini

doi:10.1016/j.bmc.2012.02.016

Favourable involvement of α _2A-adrenoreceptor antagonism in the I ₂-imidazoline binding sites-mediated morphine analgesia enhancement

Valerio Mammoli, Alessandro Bonifazi, Fabio Del Bello, Eleonora Diamanti, Mario Giannella, Alan L. Hudson, Laura Mattioli, Marina Perfumi, Alessandro Piergentili, Wilma Quaglia, Federica Titomanlio, Maria Pigini

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

44 Scopus citations

Abstract

Aim of the present study was to obtain novel α ₂- adrenoreceptor (α ₂-AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired by the non subtype-selective α ₂-AR antagonist idazoxan, we designed 1,4-dioxane derivatives bearing an aromatic area in position 5 or 6 and the imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2, with a trans stereochemical relationship between 5-phenyl and 2-imidazoline groups, was able to antagonize the sole α _2A-subtype. Moreover, 2 showed an affinity at I ₂-imidazoline binding sites (I ₂-IBS) comparable to that at α _2A-AR. In in vivo studies 2 strongly increased morphine analgesia. This interesting behaviour appeared to be induced by the favourable involvement of α _2A-AR antagonism in the I ₂-IBS-mediated morphine analgesia enhancement.

Original language	English (US)
Pages (from-to)	2259-2265
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	7
DOIs	https://doi.org/10.1016/j.bmc.2012.02.016
State	Published - Apr 1 2012
Externally published	Yes

Keywords

α -Adrenoreceptor antagonists
1,4-Dioxane nucleus
I -IBS morphine analgesia modulation
Morphine analgesia enhancement

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmc.2012.02.016

Cite this

Mammoli, V., Bonifazi, A., Del Bello, F., Diamanti, E., Giannella, M., Hudson, A. L., Mattioli, L., Perfumi, M., Piergentili, A., Quaglia, W., Titomanlio, F., & Pigini, M. (2012). Favourable involvement of α _2A-adrenoreceptor antagonism in the I ₂-imidazoline binding sites-mediated morphine analgesia enhancement. Bioorganic and Medicinal Chemistry, 20(7), 2259-2265. https://doi.org/10.1016/j.bmc.2012.02.016

Mammoli, V, Bonifazi, A, Del Bello, F, Diamanti, E, Giannella, M, Hudson, AL, Mattioli, L, Perfumi, M, Piergentili, A, Quaglia, W, Titomanlio, F & Pigini, M 2012, 'Favourable involvement of α _2A-adrenoreceptor antagonism in the I ₂-imidazoline binding sites-mediated morphine analgesia enhancement', Bioorganic and Medicinal Chemistry, vol. 20, no. 7, pp. 2259-2265. https://doi.org/10.1016/j.bmc.2012.02.016

@article{8597a40e13d8446fb9dcdc586bf1a0b5,

title = "Favourable involvement of α 2A-adrenoreceptor antagonism in the I 2-imidazoline binding sites-mediated morphine analgesia enhancement",

abstract = "Aim of the present study was to obtain novel α 2- adrenoreceptor (α 2-AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired by the non subtype-selective α 2-AR antagonist idazoxan, we designed 1,4-dioxane derivatives bearing an aromatic area in position 5 or 6 and the imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2, with a trans stereochemical relationship between 5-phenyl and 2-imidazoline groups, was able to antagonize the sole α 2A-subtype. Moreover, 2 showed an affinity at I 2-imidazoline binding sites (I 2-IBS) comparable to that at α 2A-AR. In in vivo studies 2 strongly increased morphine analgesia. This interesting behaviour appeared to be induced by the favourable involvement of α 2A-AR antagonism in the I 2-IBS-mediated morphine analgesia enhancement.",

keywords = "α -Adrenoreceptor antagonists, 1,4-Dioxane nucleus, I -IBS morphine analgesia modulation, Morphine analgesia enhancement",

author = "Valerio Mammoli and Alessandro Bonifazi and {Del Bello}, Fabio and Eleonora Diamanti and Mario Giannella and Hudson, {Alan L.} and Laura Mattioli and Marina Perfumi and Alessandro Piergentili and Wilma Quaglia and Federica Titomanlio and Maria Pigini",

year = "2012",

month = apr,

day = "1",

doi = "10.1016/j.bmc.2012.02.016",

language = "English (US)",

volume = "20",

pages = "2259--2265",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd",

number = "7",

}

TY - JOUR

T1 - Favourable involvement of α 2A-adrenoreceptor antagonism in the I 2-imidazoline binding sites-mediated morphine analgesia enhancement

AU - Mammoli, Valerio

AU - Bonifazi, Alessandro

AU - Del Bello, Fabio

AU - Diamanti, Eleonora

AU - Giannella, Mario

AU - Hudson, Alan L.

AU - Mattioli, Laura

AU - Perfumi, Marina

AU - Piergentili, Alessandro

AU - Quaglia, Wilma

AU - Titomanlio, Federica

AU - Pigini, Maria

PY - 2012/4/1

Y1 - 2012/4/1

N2 - Aim of the present study was to obtain novel α 2- adrenoreceptor (α 2-AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired by the non subtype-selective α 2-AR antagonist idazoxan, we designed 1,4-dioxane derivatives bearing an aromatic area in position 5 or 6 and the imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2, with a trans stereochemical relationship between 5-phenyl and 2-imidazoline groups, was able to antagonize the sole α 2A-subtype. Moreover, 2 showed an affinity at I 2-imidazoline binding sites (I 2-IBS) comparable to that at α 2A-AR. In in vivo studies 2 strongly increased morphine analgesia. This interesting behaviour appeared to be induced by the favourable involvement of α 2A-AR antagonism in the I 2-IBS-mediated morphine analgesia enhancement.

AB - Aim of the present study was to obtain novel α 2- adrenoreceptor (α 2-AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired by the non subtype-selective α 2-AR antagonist idazoxan, we designed 1,4-dioxane derivatives bearing an aromatic area in position 5 or 6 and the imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2, with a trans stereochemical relationship between 5-phenyl and 2-imidazoline groups, was able to antagonize the sole α 2A-subtype. Moreover, 2 showed an affinity at I 2-imidazoline binding sites (I 2-IBS) comparable to that at α 2A-AR. In in vivo studies 2 strongly increased morphine analgesia. This interesting behaviour appeared to be induced by the favourable involvement of α 2A-AR antagonism in the I 2-IBS-mediated morphine analgesia enhancement.

KW - α -Adrenoreceptor antagonists

KW - 1,4-Dioxane nucleus

KW - I -IBS morphine analgesia modulation

KW - Morphine analgesia enhancement

UR - http://www.scopus.com/inward/record.url?scp=84858297639&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858297639&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2012.02.016

DO - 10.1016/j.bmc.2012.02.016

M3 - Article

C2 - 22370341

AN - SCOPUS:84858297639

SN - 0968-0896

VL - 20

SP - 2259

EP - 2265

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 7

ER -