The present invention provides novel chimeric receptors that have unique pharmacology. In particular, the chimeric receptors comprise a mutated ligand binding domain of the alpha7 nicotinic acetylcholine receptor fused to a transmembrane or channel domain from a ligand-gated ion channel protein. The mutations in the ligand binding domain confer selective binding of compounds. Methods of using the novel chimeric receptors of the invention as well as compounds that preferentially bind and activate the chimeric receptors are also disclosed.