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.

Funding

This research was supported by NIH Grant U19DA017548.

Funders	Funder number
National Institutes of Health (NIH)
National Institute on Drug Abuse	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.",

year = "2007",

month = dec,

day = "15",

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

language = "English",

volume = "17",

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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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ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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