title: AF150(S): a new functionally selective M1 agonist improves cognitive performance in rats.
abstract: 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.
authors.affiliation: Israel Institute for Biological Research, Ness-Ziona.
authors.forename: R
authors.initials: R
authors.lastname: Brandeis
authors.forename: M
authors.initials: M
authors.lastname: Sapir
authors.forename: N
authors.initials: N
authors.lastname: Hafif
authors.forename: S
authors.initials: S
authors.lastname: Abraham
authors.forename: N
authors.initials: N
authors.lastname: Oz
authors.forename: E
authors.initials: E
authors.lastname: Stein
authors.forename: A
authors.initials: A
authors.lastname: Fisher
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001388:Aziridines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D007052:Ibuprofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001388:Aziridines; D018721:Muscarinic Agonists; D009466:Neuromuscular Blocking Agents; C065129:ibuprofen dimethyl aminoethanol octyl; C044894:ethylcholine aziridinium; D002794:Choline; D007052:Ibuprofen