Reference : Synthesis and radioligand binding studies of C-5- and C-8-substituted 1-(3,4-dimethoxybe...

	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Pharmacy, pharmacology & toxicology Physical, chemical, mathematical & earth Sciences : Chemistry
	To cite this reference:	http://hdl.handle.net/2268/2880

Title :	Synthesis and radioligand binding studies of C-5- and C-8-substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums as SK channel blockers related to N-methyl-laudanosine and N-methyl-noscapine
Language :	English
Author, co-author :	Graulich, Amaury [Université de Liège - ULg > > Chimie pharmaceutique >]
	Scuvée-Moreau, Jacqueline [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie - Département des sciences biomédicales et précliniques >]
	Seutin, Vincent [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie >]
	Liégeois, Jean-François [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
Publication date :	28-Jul-2005
Journal title :	Journal of Medicinal Chemistry
Publisher :	Amer Chemical Soc
Volume :	48
Issue/season :	15
Pages :	4972-4982
Audience :	International
ISSN :	0022-2623
City :	Washington
Abstract :	[en] The synthesis and the 125 I-apamin binding studies of original C-5- and C-8-substituted 143,4-dimethoxy-benzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums and 1-(3,4-dimethoxy-benzyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridiniums were performed in order to find a reversible and selective SK channel blocker structurally related to N-methyl-laudanosine and N-methyl-noscapine. A bulky alkyl substituent in the C-8 position of the tetrahydroisoquinoline produces a clear increase in the affinity for the apamin sensitive binding sites. The presence of an electron-withdrawing group in the C-5 and C-8 positions is not a suitable substitution for the affinity of drugs structurally related to N-methyl-laudanosine. Thiophenic analogues and 8-methoxy derivatives possess a poor affinity for the apamin sensitive binding sites. Electrophysiological studies performed with the most effective compound showed a blockade of the apamin sensitive afterhyperpolarization in rat dopaminergic neurons.
Permalink :	http://hdl.handle.net/2268/2880
	also: http://hdl.handle.net/2268/18782

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