(S)-UFR2709 is a competitive antagonist of the nicotinic acetylcholine receptor (nAChR), showing greater affinity for α4β2 nAChRs over α7 nAChRs. It effectively reduces anxiety, ethanol consumption, and ethanol preference in alcohol-preferring rats, functions as an anxiolytic agent, and holds potential for investigating nicotine addiction.

Brain nicotinic acetylcholine receptors (nAChRs) are a heterogeneous family of pentameric acetylcholine-gated cation channels, serving as molecular targets for treating alcohol abuse and dependence[1].

(S)-UFR2709 at concentrations of 50-100 μg/ml, initially exposed for 3 minutes and then held for an additional 5 minutes, leads to a reduction in bottom dwelling in the NTT test, with the compound showing a significant, dose-dependent decrease in bottom dwelling times to 52.9 and 87.0 seconds at 50 and 100 μg/ml, respectively. Additionally, (S)-UFR2709 at the same concentrations reduces nicotine-evoked mRNA expression of the α4 nACh receptor subunit in adult zebrafish, though its effect on the α4 subunit is less pronounced. When administered intraperitoneally at dosages ranging from 1-10 mg/kg daily for 17 days in high-alcohol-drinking UChB rats, (S)-UFR2709 significantly lowers ethanol consumption and preference in a dose-dependent manner, with the most successful dosage being 2.5 mg/kg, which results in a 56% reduction in alcohol consumption. This treatment does not impact the weight or locomotor behavior of the rats.