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

NS3861 fumarate demonstrates selectivity by activating α3-containing nicotinic acetylcholine receptors (nAChRs) while showing no activation in α4-containing receptors in HEK293 cell lines. It exhibits a clear preference, acting as a stronger agonist on α3β2 receptors (EC 50 of 0.15 μM) compared to α3β4 receptors (EC 50 of 1.7 μM) and possesses high affinity and partial agonist characteristics for α3β4-expressed nAChRs [2]. This compound presents an inverse β-subunit preference, emphasizing its distinctive interaction with nAChR subtypes [1].

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