Methyllycaconitine analogues have mixed antagonist effects at nicotinic acetylcholine receptors.
Bicyclic analogues of methyllycaconitine (MLA), such as 12, have been synthesised that incorporate the C1-OMe substituent present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) were conducted on these analogues and a related tricyclic analogue 2. The most potent compound, 2, was an antagonist at all receptors studied but displayed different antagonist effects at each receptor subtype. This study more clearly defines the biological effects of MLA analogues at nAChRs and demonstrates that these analogues are not selective ligands for the alpha7 nAChR subtype.
Barker
David
D
School of Chemistry, F11, University of Sydney, Camperdown, NSW 2006, Australia.
Lin
Diana H-S
DH
Carland
Jane E
JE
Chu
Cindy P-Y
CP
Chebib
Mary
M
Brimble
Margaret A
MA
Savage
G Paul
GP
McLeod
Malcolm D
MD
D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D014981:Xenopus
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D000157:Aconitine