In vitro and in vivo characterization of [125I]iodomethyllycaconitine in the rat

The in vitro and in vivo binding characteristics of [125I]iodomethyllycaconitine ([125I]iodoMLA) were determined in the rat. [125I]iodoMLA binding to rat cerebral cortex membranes was saturable and reversible and its specific binding represented approximately 70-80% of the total binding. [125I]iodoMLA labeled a single site with Kd = 1.8 +/- 0.4 nM and Bmax = 68 +/- 3 fmol/mg protein. Kinetic analysis revealed a t1/2 for association and dissociation of 10.5 +/- 3.1 and 10.3 +/- 1.6 min, respectively. Pharmacological characterization of [125I]iodoMLA binding indicated that it was specific for the alpha7 nAChR. In vitro brain region binding studies revealed greater binding in regions known to contain high numbers of alpha7 nAChRs. The analysis of the biodistribution of intravenously administered [125I]iodoMLA indicated that it was rapidly cleared and exhibited poor brain penetration; nevertheless, the levels of [125I]iodoMLA in alpha7 nAChR-rich target regions were significantly increased compared to the nontarget region (cerebellum) 60-120 min after administration. No metabolism of MLA by human liver S9 fraction was detected. Our results suggest that [125I]iodoMLA will be a useful radioligand to study the alpha7 nAChR in vitro and in vivo.