A novel derivative of xanomeline improved memory function in aged mice.
- Author:
Yi-Hui CUI
1
;
Wen SI
;
Liang YIN
;
Shu-Ming AN
;
Jing JIN
;
Shi-Ning DENG
;
Xiao-Hua CAO
Author Information
- Publication Type:Journal Article
- MeSH: Aging; drug effects; Animals; Brain; drug effects; Dose-Response Relationship, Drug; Excitatory Postsynaptic Potentials; drug effects; Lethal Dose 50; Long-Term Potentiation; drug effects; Memory; drug effects; Mice; Muscarinic Agonists; administration & dosage; adverse effects; Pyridines; administration & dosage; adverse effects; chemistry; Thiadiazoles; administration & dosage; adverse effects; chemistry
- From:Neuroscience Bulletin 2008;24(4):251-257
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo characterize the function of a new xanomeline-derived M1 agonist, 3-[3-(3-florophenyl-2-propyn-1-ylthio)-1,2,5-thiadiazol-4-yl]-1,2,5,6- tetrahydro-1-methylpyridine Oxalate (EUK1001), the acute toxicity and the effects on synaptic plasticity and cognition of EUK1001 were evaluated.
METHODSTo examine the median lethal dose (LD50) of EUK1001, a wide dose range of EUK1001 was administered by p.o. and i.p. in aged mice. Furthermore, novel object recognition task and in vitro electrophysiological technique were utilized to investigate the effects of EUK1001 on recognition memory and hippocampal synaptic plasticity in aged mice.
RESULTSEUK1001 exhibited lower toxicity than xanomeline, and improved the performance of aged mice in the novel object recognition test. In addition, bath application of 1 micromol/L EUK1001 directly induced long-term potentiation in the hippocampus slices.
CONCLUSIONWe conclude that EUK1001 can improve the age-related cognitive deficits.
