NS3861 fumarate is an agonist of nicotinic acetylcholine receptors (nAChRs). NS3861 fumarate is a partial agonist at α3β4 nAChR and binds with high affinity to heteromeric α3β4 nAChR. The binding Ki values of 0.62, 25, 7.8, 55 nM for α3β4, α3β2, α4β4, α4β2, respectively[1].

NS3861 fumarate shows the opposite β-subunit preference and a complete lack of activation at α4-containing receptors in HEK293 cell lines. NS3861 fumarate selectively activates α3- but not α4-containing nAChRs and it displays higher efficacy at the α3β2 receptor compared with the α3β4 receptor, with EC 50 s of 1.7 and 0.15 μM for α3β2 and α3β4 receptor, respectively [1]. NS3861 fumarate shows high affinity and partial agonist properties in α3β4-expressed nAChRs [2].

NS3861 fumarate dose-dependently enhances fecal pellet expulsion in mice that received long-term morphine treatment [2].