Table II. Binding Characteristics of nAChRs ligands against 150pM [³H]Epibatidine.

Binding of A-84543, its analogs, and A-85380 was compared to that of nicotine and the nicotinic β2 receptor antagonist DHβE in cerebral cortical rat membrane homogenates (10 mg) in a total volume of 1 ml for 4 hr at 24°C. The inhibition constants (K_i) were calculated using the Cheng-Prusoff equation from measured IC₅₀s and a K_D value of 35pM for [³H]EB from the saturation experiments. The values presented are the average of n = 3–6 independent experiments per ligand run in triplicates. Ligand binding was determined for each new compound as the hydrobromide (HBr) salt (H-11MNH, H-11ONH, and H-11PNH) or as the synthesized base (A-84543, and H-11ONM); while nicotine was used as the hydrogen tartrate salt.

	IC50		Ki
	nM		nM
DRUGS	AVG	SEM	AVG	SEM	n
A-85380	2.09	0.38	0.37	0.06	4
H-11MNH2	2.51	0.59	0.46	0.11	5
A-84543	17.90	1.95	3.44	0.40	5
Nicotine	32.30	9.85	5.99	1.44	5
DHβE	344.67	42.22	61.33	5.89	3
H-11ONH	115,000	41,845	21,800	7,971	6
H-11PNH	303,000	75,850	59,200	16,722	5
H-11ONM	322,700	98,342	60,300	18,880	6

²This work represents new syntheses and new data of the A-85380 2a analog A84543 and the 3a analog, here named H-11MNH, that complements work originally done by Abreo et al. [22].