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.
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.
Authors: N C Bodick; W W Offen; A I Levey; N R Cutler; S G Gauthier; A Satlin; H E Shannon; G D Tollefson; K Rasmussen; F P Bymaster; D J Hurley; W Z Potter; S M Paul Journal: Arch Neurol Date: 1997-04
Authors: Antonella Caccamo; Salvatore Oddo; Lauren M Billings; Kim N Green; Hilda Martinez-Coria; Abraham Fisher; Frank M LaFerla Journal: Neuron Date: 2006-03-02 Impact factor: 17.173
Authors: Jason M Uslaner; Donnie Eddins; Vanita Puri; Christopher E Cannon; Jane Sutcliffe; Chan Sing Chew; Michelle Pearson; Jeffrey A Vivian; Ronald K Chang; William J Ray; Scott D Kuduk; Marion Wittmann Journal: Psychopharmacology (Berl) Date: 2012-07-24 Impact factor: 4.530
Authors: Caterina Montani; Carola Canella; Adam J Schwarz; Jennifer Li; Gary Gilmour; Alberto Galbusera; Keith Wafford; Daniel Gutierrez-Barragan; Andrew McCarthy; David Shaw; Karen Knitowski; David McKinzie; Alessandro Gozzi; Christian Felder Journal: Neuropsychopharmacology Date: 2020-12-20 Impact factor: 7.853