Neuronal α4β2 nicotinic cholinergic receptors are the major high affinity nAChRs in the mammalian brain and mediate much of the dopamine releasing and cognition-enhancing effects of nicotine in the brain. Although many nicotine analogs have been synthesized and their α4β2 nAChR affinities measured by various labs, the functional properties of many of these compoundswere not investigated. We previously reported the binding affinities of several nicotine analogs for both rat α4*β2 and α7 nAChRs (Wildeboer et al., 2003, SFN Mtg Abstr. 158.6). Here we report the functional properties of these same analogs when tested on the human α4β2 nAChR. Membrane depolarizing effects on tsA201 cells (provided by J. Lindstrom, U. Penn.) were measured using a Molecular Devices fluorescent dye. The signals were normalized using a KCl calibrant and responses were expressed relative to the maximal response produced by nicotine. The maximal responses of all compounds including nicotine were always much smaller than the KCl depol...