The α4β2 nAChR is the most abundant nAChR in the CNS, where it is known to exist in two distinct stochiometries, (α4)2(β2)3 and (α4)3(β2)2. The latter, which is also the most abundant, has recently been shown to contain an additional third unique acetylcholine binding site in the interface between two α4 subunits and we have suggested that compounds selectively targeting this site could work as allosteric modulators.1 We present results from a high throughput virtual screening project aimed at identifying such compounds. 5 million commercially available compounds were screened in homology models of the α4α4 and α4β2 dimers. Subsequently, hits were filtered according to docking scores and specific receptor interactions expected to provide stoichiometry selectivity. 23 Compounds were purchased and initial screening has yielded 6 actives. Interestingly several of the identified hits are structural hybrids comprising motives from classical nAChR agonist and motives from known allosteric modulators. The high hit-rate shows that virtual screening techniques can successfully contribute to early hit finding projects.