(±)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3′) quinuclidine (AF102B): A new M1 agonist attenuates cognitive dysfunctions in AF64A-treated rats

A. Fisher, R. Brandeis, Z. Pittel, I. Karton, M. Sapir, S. Dachir, A. Levy, E. Heldman

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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.

Original languageEnglish
Pages (from-to)325-331
Number of pages7
JournalNeuroscience Letters
Volume102
Issue number2-3
DOIs
StatePublished - 31 Jul 1989
Externally publishedYes

Keywords

  • AF102B
  • AF64A
  • Alzheimer's disease
  • Animal model
  • Cholinergic hypofunction
  • M muscarinic agonist

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