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: R Brandeis, M Sapir, N Hafif, S Abraham, N Oz, E Stein, A Fisher
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 51 Issue 4 Pg. 667-74 (Aug 1995) ISSN: 0091-3057 [Print] United States
• PMID: 7675841 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Aziridines
• Muscarinic Agonists
• Neuromuscular Blocking Agents
• ibuprofen dimethyl aminoethanol octyl
• ethylcholine aziridinium
• Choline
• Ibuprofen

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Avoidance Learning (drug effects)
• Aziridines (antagonists & inhibitors, pharmacology)
• Choline (analogs & derivatives, antagonists & inhibitors, pharmacology)
• Cognition (drug effects)
• Exploratory Behavior (drug effects)
• Ibuprofen (analogs & derivatives, pharmacology)
• Male
• Maze Learning (drug effects)
• Memory (drug effects)
• Muscarinic Agonists (pharmacology)
• Neuromuscular Blocking Agents (antagonists & inhibitors, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Stimulation, Chemical