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

• Published in: Pharmacology, biochemistry and behavior Vol. 51; no. 4; pp. 667 - 674
• Main Authors: BRANDEIS, R, SAPIR, M, HAFIF, N, ABRAHAM, S, OZ, N, STEIN, E, FISHER, A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01.08.1995
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Avoidance Learning - drug effects; Aziridines - antagonists & inhibitors; Aziridines - pharmacology; Biological and medical sciences; Choline - analogs & derivatives; Choline - antagonists & inhibitors; Choline - pharmacology; Cognition - drug effects; Exploratory Behavior - drug effects; Ibuprofen - analogs & derivatives; Ibuprofen - pharmacology; Male; Maze Learning - drug effects; Medical sciences; Memory - drug effects; Muscarinic Agonists - pharmacology; Neuromuscular Blocking Agents - antagonists & inhibitors; Neuromuscular Blocking Agents - pharmacology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Stimulation, Chemical; Memory disorder; Nervous system diseases; Cognitive disorder; Rat; Psychotropic; Treatment efficiency; Rodentia; Oral administration; Cerebral disorder; Parasympathomimetic; Vertebrata; Chemotherapy; Mammalia; Animal; Nootropic agent; Central nervous system disease; Neurological disorder
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(94)00435-L

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.