The nAChR is unusual among receptors in that agonist-induced desensitization leads to an up-regulation of the receptor. Ligand interactions occur with various discrete forms of the receptor as originally proposed in 1958 by Katz and Thesleff, e.g., open, resting, and desensitized states that are in equilibrium (Lena and Changeux, 1993). In addition to the acetylcholine (ACh) binding site, the nAChR, like other LGICs, e.g., GABAA(benzodiazepine, neurosteroid, and barbiturate) andN-methyl-D-aspartate (glycine and polyamine), has binding sites for other types of ligand that can modify the equilibrium between the receptor states thus representing the classical allosteric receptor. Site-directed mutagenesis has shown that the binding site(s) for cholinergic agonists e.g., ACh, (−)-nicotine, cytisine, and antagonists, e.g., neuronal bungarotoxin (n-BgT), dihydro-β-erythroidine…