PF-4575180

PF-4575180 is a **small molecule azabicyclic compound** developed by Pfizer as a **selective partial agonist** for the α3β4 subtype of the **neuronal nicotinic acetylcholine receptor (nAChR)**. It was designed to selectively target the α3β4 nAChR with **high affinity and intrinsic activity**, while showing minimal activity at α4β2 and α7 nAChRs[1][2]. PF-4575180’s mechanism—partial activation and likely stabilization of the desensitized state of the α3β4 nAChR—makes it of interest for the treatment of **substance use disorders**, particularly **alcohol use disorder**. In preclinical animal models, PF-4575180 has been shown to **selectively reduce ethanol (alcohol) self-administration** and voluntary ethanol consumption without significantly affecting sucrose consumption or total fluid intake[1][2][4][5][7][8][9]. Its pharmacology is related to, but more selective than, varenicline, an approved smoking cessation agent.