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.