(+)-Laburnamine, a Natural Selective Ligand and Partial Agonist for the α4β2 Nicotinic Receptor Subtype

(+)-Laburnamine (1), a rare alkaloid extracted from Laburnum anagyroides seeds (similar to 4 mg from 1 kg), was shown to bind with high affinity (K-i, 293 nM) to the alpha 4 beta 2 nicotinic receptor subtype, which is, respectively, 126 and 136 times higher than to the alpha 3 beta 4 (K-i 37 mu M) and alpha 7 subtypes (K-i 40 mu M). When its ability to release [H-3]-dopamine from striatal slices was tested in a functional assay, compound 1 behaved as a partial agonist with an EC50 of 5.8 mu M and an E-max that was 43% that of nicotine. When incubated with nicotine in the same assay, 1 prevented a maximal effect from being reached.