Abstract Inhibitors bearing the imidazole, adamantane and related structures were synthesized and tested against WT, S31N and S31N-L26I mutant M2 channels. Although amantadine (1) only inhibited WT M2 channel, compound 6 containing the imidazole and adamantane groups showed good inhibitory activity to WT and mutant M2 channels. The stereochemistry and basic pK a of α-amine are important for the activity of inhibitors and ...