ABT-107, a selective α7 neuronal nicotinic receptor agonist, demonstrates neuroprotective effects against nigrostriatal damage in rats with unilateral 6-hydroxydopamine lesions.

ABT-107 demonstrates strong bioavailability and CNS penetration across different species, including mice, rats, and monkeys, with variable oral and injection-based absorption rates (mice: orally 51.1%, intraperitoneally 100%; rats: orally 81.2%, intraperitoneally 100.0%; monkeys: orally 40.6%, intramuscularly 100%). It effectively increases ERK1/2 and CREB levels in a dose-dependent manner when administered intraperitoneally at doses ranging from 0.01 to 1 μmol/kg, 15 minutes before sacrifice. Additionally, at doses of 0.01, 0.1, and 1.0 mg/kg intraperitoneally, ABT-107 enhances S 9 -GSK3 activity and reduces p-tau in the mouse cortex and hippocampus. A daily intraperitoneal infusion of 5 mg/kg effectively mitigates tau hyperphosphorylation in AD transgenic APP-tau mice. In Sprague-Dawley male rats (350-380 g), daily intraperitoneal injections of 1 and 3 μmol/kg for three consecutive days significantly increase ACh release by day 3, suggesting a dose-dependent relationship and the necessity of higher doses for naive rats not exhibiting cognitive-related behavior. Furthermore, in female TAPP mice and their wild-type littermates, a continuous subcutaneous infusion of 1 mg/kg for two weeks elevates Ser9 phosphorylation in the cingulate cortex 15 minutes after acute administration, exhibiting the compound's pharmacodynamic effects in both induced and naturalistic animal models.