title: A novel derivative of xanomeline improved memory function in aged mice.
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.
  
  
  CONCLUSIONS
  We conclude that EUK1001 can improve the age-related cognitive deficits.
authors.affiliation: Shanghai Institute of Brain Functional Genomics, the Key Laboratories of Ministry of Education of China and Shanghai Municipality, East China Normal University, Shanghai, China.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Cui
authors.forename: Wen
authors.initials: W
authors.lastname: Si
authors.forename: Liang
authors.initials: L
authors.lastname: Yin
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: An
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Shi-Ning
authors.initials: SN
authors.lastname: Deng
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Cao
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007928:Lethal Dose 50; D017774:Long-Term Potentiation / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018721:Muscarinic Agonists / Q000008:administration & dosage* / Q000009:adverse effects*; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000737:chemistry; D013830:Thiadiazoles / Q000008:administration & dosage* / Q000009:adverse effects* / Q000737:chemistry
chemical_list: C533736:3-(3-(3-florophenyl-2-propyn-1-ylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6- tetrahydro-1-methylpyridine oxalate; D018721:Muscarinic Agonists; D011725:Pyridines; D013830:Thiadiazoles; C075257:xanomeline