Figure 2.

Partial agonism of human α7- or α9α10-nAChRs by compounds 2, 6, 28, or 33 (applied alone). Compounds 2, 6, 28, and 33 were selected (please see the test for criteria) to determine whether they were able to activate human α7- or α9α10-nAChR (intrinsic activity). Two-electrode voltage clamp protocols were similar to those used in Figure 1, including the use of an initial train of ACh (1 mM) control pulses to ensure the stability of responses and collect positive control data for a full agonist. After a further 1 min wash period, compounds of interest were applied for 1 s at 100 μM (the same as the highest concentration applied in Figure 1; in this case, test compounds were applied alone instead of coapplied with ACh). In this case, responses at both α7- and α9α10-nAChR were quantified in terms of both peak currents and AUC. For each individual oocyte, and for each method of quantification, responses when test compounds were coapplied were normalized to the mean of the magnitude of the final two positive control responses that preceded the introduction of the test compound. Each bar represents the mean response collected from three individual oocytes, with error bars representing the S.E.M. Points represent responses from individual oocytes.