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Neurosci Bull. 2008 Aug;24(4):251-7. doi: 10.1007/s12264-008-0204-5.

A novel derivative of xanomeline improved memory function in aged mice.

Author information

1
Shanghai Institute of Brain Functional Genomics, the Key Laboratories of Ministry of Education of China and Shanghai Municipality, East China Normal University, Shanghai, China.

Abstract

OBJECTIVE:

To 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.

METHODS:

To 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.

RESULTS:

EUK1001 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.

CONCLUSION:

We conclude that EUK1001 can improve the age-related cognitive deficits.

PMID:
18668154
PMCID:
PMC5552585
DOI:
10.1007/s12264-008-0204-5
[Indexed for MEDLINE]
Free PMC Article

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