TY - JOUR
T1 - A novel derivative of xanomeline improved memory function in aged mice
AU - Cui, Yi Hui
AU - Si, Wen
AU - Yin, Liang
AU - An, Shu Ming
AU - Jin, Jing
AU - Deng, Shi Ning
AU - Cao, Xiao Hua
PY - 2008/8
Y1 - 2008/8
N2 - 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 μmol/L EUK1001 directly induced long-term potentiation in the hippocampus slices. Conclusion: We conclude that EUK1001 can improve the agerelated cognitive deficits.
AB - 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 μmol/L EUK1001 directly induced long-term potentiation in the hippocampus slices. Conclusion: We conclude that EUK1001 can improve the agerelated cognitive deficits.
KW - EUK1001
KW - Hippocampus
KW - LD50
KW - Long-term potentiation
KW - Memory
KW - Xanomeline
UR - https://www.scopus.com/pages/publications/48749112833
U2 - 10.1007/s12264-008-0204-5
DO - 10.1007/s12264-008-0204-5
M3 - 文章
C2 - 18668154
AN - SCOPUS:48749112833
SN - 1673-7067
VL - 24
SP - 251
EP - 257
JO - Neuroscience Bulletin
JF - Neuroscience Bulletin
IS - 4
ER -