3-(4-Hydroxyphenyl-1,2,3-Triazol-1-yl)Quinuclidine, a Selective α7 Nicotinic Acetylcholine Receptor Agonist, Attenuates Inflammatory Pain with a Favorable Central Nervous System Safety Profile in Mice

Selective α7 nicotinic acetylcholine receptors (α7 nAChRs) have emerged as therapeutic targets for managing various pain conditions, including inflammatory pain. Activation of α7 nAChRs by selective agonists has been shown to exert both antinociceptive and anti-inflammatory effects. In this study, we investigate the pharmacological effects of 3-(4-Hydroxyphenyl-1,2,3-triazol-1-yl)-quinuclidine (QND8), a selective and potent α7 nAChR agonist, in a murine model of carrageenan-induced inflammatory pain and evaluated its central nervous system (CNS) safety profile. QND8 significantly alleviated thermal and mechanical hyperalgesia at doses of 1, 3, and 10 mg/kg, and reduced carrageenan-induced paw edema at doses of 10 mg/kg. Importantly, QND8 exhibited these effects without impairing motor coordination and general behaviors, as demonstrated by the rotarod test and automated home cage behavioral analysis. These findings highlight QND8 as a promising preclinical analgesic candidate with anti-inflammatory efficacy and a favorable CNS safety profile. Computational modeling further revealed a stable and high-affinity binding of QND8 within the orthosteric site of α7 nAChR, consistent with its selective agonist activity. The results support further development of QND8 as a selective α7 nAChR-targeting therapeutic for inflammatory pain.