Carbamoylcholine homologs: synthesis and pharmacology at nicotinic acetylcholine receptors

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Anders A. Jensen, Ivan Bisgaard Mikkelsen, Bente Frølund, Karla Frydenvang, Lotte Brehm, Jerzy W Jaroszewski, Hans Bräuner-Osborne, Erik Falch, Povl Krogsgaard-Larsen

In a recent study, racemic 3-(N,N-dimethylamino)butyl-N,N-dimethylcarbamate (1) was shown to be a potent agonist at neuronal nicotinic acetylcholine receptors with a high selectivity for nicotinic over muscarinic acetylcholine receptors [Mol. Pharmacol. 64 (2003) 865-875]. Here we present the synthesis and pharmacological characterization of a series of analogs of, where the methyl group at C-3 has been replaced by different alkyl substituents. Ring systems have been incorporated into the carbon backbone of some of the molecules, or the amino group has been build into ring systems. Furthermore, the (+)- and (-)-enantiomers of have been separated, and X-ray crystallography has revealed that (-)-1 possesses (S)-configuration. The compounds have been characterized pharmacologically at recombinant nicotinic receptor subtypes. The structure-activity relationship study has provided valuable insight into the mode of interactions of and its analogs with neuronal nicotinic acetylcholine receptors.
Original languageEnglish
JournalEuropean Journal of Pharmacology
Volume497
Issue number2
Pages (from-to)125-37
Number of pages13
ISSN0014-2999
DOIs
Publication statusPublished - 2004

    Research areas

  • Animals, Carbachol, Cell Line, Dose-Response Relationship, Drug, Humans, Protein Binding, Rats, Receptors, Nicotinic, Structure-Activity Relationship

ID: 38484890