AF150(S): a new functionally selective M1 agonist improves cognitive performance in rats

This study was aimed at evaluating the ability of a new functionally selective partial M1 agonist, AF150(S), to reverse cognitive impairments in rats. A memory deficits-induced animal model was used that involved AF64A (3 nmol/2 microliters/side) bilaterally injected ICV. AF150(S) was administered PO. The pharmacodynamic profile of the compound was established and its general toxicity was evaluated. Animals were tested on three behavioral tasks: step-through passive avoidance, Morris water maze reference memory paradigm, and radial arm maze working memory paradigm. The sign-free dose of AF150(S) was > 40 mg/kg whereas the LD50 was > 500 mg/kg. In comparison, the effective dose in reversing performance impairments on the various tasks was much lower (0.5-5 mg/kg). The data suggest that AF150(S) possesses potential cognitive enhancement abilities, probably due to a specific increase of cholinergic function.