Beneficial effects of FKS-508 (AF102B), a selective M1 agonist, on the impaired working memory in AF64A-treated rats.

Abstract

The effects of FKS-508 [AF102B; cis-2-methylspiro(1,3-oxathiolane-5,3')quinuclidine], a selective M1 muscarinic receptor agonist, were examined to predict the possible activity on memory disorders using a T-maze and radial-arm maze task in experimental amnesia models. The amnesia models were produced by bilateral intracerebroventricular injection of ethylcholine aziridinium ion (AF64A), a selective cholinotoxin, in rats. Repeated administrations of FKS-508 (5 mg/kg/day, i.p.) for 5 weeks significantly ameliorated impaired performance of AF64A-treated rats (AF64A-rats) in a delayed alternation task in the T-maze. Repeated administrations of FKS-508 (1 and 5 mg/kg/day, p.o.) for 5 weeks significantly ameliorated acquisition failures of AF64A-rats in a radial-arm maze task. Single administration of FKS-508 (1 and 5 mg/kg, p.o.) significantly reduced the incorrect choices of AF64A-rats in a radial-arm maze task with 6 hr-delay time. No abnormalities in general behaviors, such as loss of appetite and ataxia, were observed in rats treated with FKS-508 repeatedly during 5 weeks. Our present results showed that FKS-508 can ameliorate memory impairments in AF64A-rats with central cholinergic hypofunction without causing any behavioral abnormalities. FKS-508 may be considered as a candidate for the clinical examination of the cholinergic hypothesis of senile dementia of the Alzheimer type.

• Authors: N Nakahara, Y Iga, Y Saito, F Mizobe, G Kawanishi
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 51 Issue 4 Pg. 539-47 (Dec 1989) ISSN: 0021-5198 [Print] Japan
• PMID: 2615046 (Publication Type: Journal Article)

Chemical References

• Aziridines
• Neuromuscular Blocking Agents
• Parasympathomimetics
• Quinuclidines
• Receptors, Muscarinic
• Thiophenes
• Oxotremorine
• ethylcholine aziridinium
• Choline O-Acetyltransferase
• cevimeline
• Choline

Topics

• Animals
• Aziridines (pharmacology)
• Cerebral Cortex (drug effects, enzymology)
• Choline (analogs & derivatives, pharmacology)
• Choline O-Acetyltransferase (metabolism)
• Hippocampus (drug effects, enzymology)
• Learning (drug effects)
• Male
• Memory (drug effects)
• Neuromuscular Blocking Agents (pharmacology)
• Oxotremorine (pharmacology)
• Parasympathomimetics (pharmacology)
• Quinuclidines (pharmacology)
• Rats
• Rats, Inbred Strains
• Receptors, Muscarinic (drug effects)
• Thiophenes