Synthesis and nicotinic receptor activity of a hydroxylated tropane.
(+/-)-3alpha-hydroxy homoepibatidine 4 has been synthesized from the alkaloid scopolamine 5 and its properties as a nicotinic agonist assessed. While still binding strongly, the compound showed reduced agonist potency for the alpha(4)beta(2) nAChR compared with the parent compound epibatidine 1. Compound 4 also displayed generally similar binding and selectivity profiles at alpha(4)beta(2), alpha(2)beta(4), alpha(3)beta(4), and alpha(4)beta(4) nAChR subtypes to those for nicotine.
Bremner
John B
JB
Department of Chemistry and Institute for Biomolecular Science, University of Wollongong, Wollongong, NSW 2522, Australia. john_bremner@uow.edu.au
Godfrey
Colette A
CA
Jensen
Anders A
AA
Smith
Reginald J
RJ
D000818:Animals; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects; D018722:Nicotinic Agonists / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014326:Tropanes / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D014326:Tropanes