228867-09-2Relevant articles and documents
Design, synthesis and discovery of picomolar selective α4β2 nicotinic acetylcholine receptor ligands
Yenugonda, Venkata M.,Xiao, Yingxian,Levin, Edward D.,Rezvani, Amir H.,Tran, Thao,Al-Muhtasib, Nour,Sahibzada, Niaz,Xie, Teresa,Wells, Corinne,Slade, Susan,Johnson, Joshua E.,Dakshanamurthy, Sivanesan,Kong, Hye-Sik,Tomita, York,Liu, Yong,Paige, Mikell,Kellar, Kenneth J.,Brown, Milton L.
, p. 8404 - 8421 (2013/12/04)
Developing novel and selective compounds that desensitize α4β2 nicotinic acetylcholine receptors (nAChRs) could provide new effective treatments for nicotine addiction, as well as other disorders. Here we report a new class of nAChR ligands that display high selectivity and picomolar binding affinity for α4β2 nicotinic receptors. The novel compounds have Ki values in the range of 0.031-0.26 nM and properties that should make them good candidates as drugs acting in the CNS. The selected lead compound 1 (VMY-2-95) binds with high affinity and potently desensitizes α4β2 nAChRs. At a dose of 3 mg/kg, compound 1 significantly reduced rat nicotine self-administration. The overall results support further characterizations of compound 1 and its analogues in preclinical models of nicotine addiction and perhaps other disorders involving nAChRs.
