(+-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3') quinuclidine (AF102B): a new M1 agonist attenuates cognitive dysfunctions in AF64A-treated rats.

Abstract

(+-)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3')quinuclidine (AF102B), a new muscarinic agonist of utmost rigidity, exhibits a high selectivity for M1 muscarinic receptors. In rats having a cholinergic hypofunction induced by the intracerebroventricular administration of ethylcholine aziridinium (AF64A), AF102B reversed cognitive impairments in a step-through passive avoidance task and in an 8-arm radial maze. AF102B reversed cognitive impairments at significantly lower doses than those needed to induce side-effects. In addition, AF102B exhibited low toxicity. The results suggest that AF102B may prove useful for treatments of cholinergic deficiencies and cognitive impairments, like those reported in Alzheimer's disease.

• Authors: A Fisher, R Brandeis, Z Pittel, I Karton, M Sapir, S Dachir, A Levy, E Heldman
• Journal: Neuroscience letters (Neurosci Lett) Vol. 102 Issue 2-3 Pg. 325-31 (Jul 31 1989) ISSN: 0304-3940 [Print] Ireland
• PMID: 2812509 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aziridines
• Parasympathomimetics
• Quinuclidines
• Receptors, Muscarinic
• Thiophenes
• ethylcholine aziridinium
• cevimeline
• Choline

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Animals
• Aziridines (pharmacology)
• Behavior, Animal (drug effects)
• Choline (pharmacology)
• Cognition Disorders (chemically induced, drug therapy, metabolism)
• Disease Models, Animal
• Drug Design
• Male
• Molecular Structure
• Parasympathomimetics (pharmacology)
• Quinuclidines (pharmacology, therapeutic use)
• Rats
• Rats, Inbred Strains
• Receptors, Muscarinic (metabolism)
• Thiophenes