tris-Azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release

Guangrong Zheng; Sangeetha P. Sumithran; Agripina G. Deaciuc; Linda P. Dwoskin; Peter A. Crooks

doi:10.1016/j.bmcl.2007.10.062

tris-Azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release

Guangrong Zheng, Sangeetha P. Sumithran, Agripina G. Deaciuc, Linda P. Dwoskin, Peter A. Crooks

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

15 Scopus citations

Abstract

A series of tris-azaaromatic quaternary ammonium salts has been synthesized and evaluated for their ability to inhibit neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked [³H]dopamine release from superfused rat striatal slices and for inhibition of [³H]nicotine and [³H]methyllycaconitine binding to whole rat brain membranes. The 3-picolinium compound 1,3,5-tri-{5-[1-(3-picolinium)]-pent-1-ynyl}benzene tribromide (tPy3PiB), 3b, exhibited high potency and selectivity for nAChR subtypes mediating nicotine-evoked [³H]dopamine release with an IC₅₀ of 0.2 nM and I_max of 67%.

Original language	English
Pages (from-to)	6701-6706
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2007.10.062
State	Published - Dec 15 2007

Bibliographical note

Funding Information:
This research was supported by NIH Grant U19DA017548.

Keywords

Dopamine release
Nicotine
Nicotinic acetylcholine receptor
tris-Azaaromatic quaternary ammonium

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2007.10.062

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title = "tris-Azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release",

abstract = "A series of tris-azaaromatic quaternary ammonium salts has been synthesized and evaluated for their ability to inhibit neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked [3H]dopamine release from superfused rat striatal slices and for inhibition of [3H]nicotine and [3H]methyllycaconitine binding to whole rat brain membranes. The 3-picolinium compound 1,3,5-tri-{5-[1-(3-picolinium)]-pent-1-ynyl}benzene tribromide (tPy3PiB), 3b, exhibited high potency and selectivity for nAChR subtypes mediating nicotine-evoked [3H]dopamine release with an IC50 of 0.2 nM and Imax of 67%.",

keywords = "Dopamine release, Nicotine, Nicotinic acetylcholine receptor, tris-Azaaromatic quaternary ammonium",

author = "Guangrong Zheng and Sumithran, {Sangeetha P.} and Deaciuc, {Agripina G.} and Dwoskin, {Linda P.} and Crooks, {Peter A.}",

note = "Funding Information: This research was supported by NIH Grant U19DA017548.",

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month = dec,

day = "15",

doi = "10.1016/j.bmcl.2007.10.062",

language = "English",

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tris-Azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release. / Zheng, Guangrong; Sumithran, Sangeetha P.; Deaciuc, Agripina G. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 24, 15.12.2007, p. 6701-6706.

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

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T1 - tris-Azaaromatic quaternary ammonium salts

T2 - Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release

AU - Zheng, Guangrong

AU - Sumithran, Sangeetha P.

AU - Deaciuc, Agripina G.

AU - Dwoskin, Linda P.

AU - Crooks, Peter A.

N1 - Funding Information: This research was supported by NIH Grant U19DA017548.

PY - 2007/12/15

Y1 - 2007/12/15

N2 - A series of tris-azaaromatic quaternary ammonium salts has been synthesized and evaluated for their ability to inhibit neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked [3H]dopamine release from superfused rat striatal slices and for inhibition of [3H]nicotine and [3H]methyllycaconitine binding to whole rat brain membranes. The 3-picolinium compound 1,3,5-tri-{5-[1-(3-picolinium)]-pent-1-ynyl}benzene tribromide (tPy3PiB), 3b, exhibited high potency and selectivity for nAChR subtypes mediating nicotine-evoked [3H]dopamine release with an IC50 of 0.2 nM and Imax of 67%.

AB - A series of tris-azaaromatic quaternary ammonium salts has been synthesized and evaluated for their ability to inhibit neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked [3H]dopamine release from superfused rat striatal slices and for inhibition of [3H]nicotine and [3H]methyllycaconitine binding to whole rat brain membranes. The 3-picolinium compound 1,3,5-tri-{5-[1-(3-picolinium)]-pent-1-ynyl}benzene tribromide (tPy3PiB), 3b, exhibited high potency and selectivity for nAChR subtypes mediating nicotine-evoked [3H]dopamine release with an IC50 of 0.2 nM and Imax of 67%.

KW - Dopamine release

KW - Nicotine

KW - Nicotinic acetylcholine receptor

KW - tris-Azaaromatic quaternary ammonium

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tris-Azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release

Abstract

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Keywords

ASJC Scopus subject areas

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