PD 142505-0028 (or CI-1017) is a functionally M1-selective muscarinic agonist. It rapidly increases glutamate but not aspartate concentrations in the striatum of anesthetized rats. improved spatial memory of hippocampally deficient mice and nbM-lesioned rats at doses of 1.0-3.2 and 0.1-0.3 mg/kg, respectively, while producing parasympathetic side effects only at very high doses (100-178 mg/kg). Additionally, CI-1017 inhibited production of amyloidogenic A beta and increased secretion of soluble APP. Thus, CI-1017, besides treating AD symptomatically, may also retard its progression. References: Tecle H, Schwarz RD, Barrett SD, Callahan MJ, Caprathe BW, Davis RE, Doyle P, Emmerling M, Lauffer DJ, Mirzadegan T, Moreland DW, Lipiniski W, Nelson C, Raby C, Spencer C, Spiegel K, Thomas AJ, Jaen JC. CI-1017, a functionally M1-selective muscarinic agonist: design, synthesis, and preclinical pharmacology. Pharm Acta Helv. 2000 Mar;74(2-3):141-8. PubMed PMID: 10812951. 2: Weiss C, Preston AR, Oh MM, Schwarz RD, Welty D, Disterhoft JF. The M1 muscarinic agonist CI-1017 facilitates trace eyeblink conditioning in aging rabbits and increases the excitability of CA1 pyramidal neurons. J Neurosci. 2000 Jan 15;20(2):783-90. PubMed PMID: 10632607. 3: Ros E, Aleu J, Marsal J, Solsona C. Effects of CI-1002 and CI-1017 on spontaneous synaptic activity and on the nicotinic acetylcholine receptor of Torpedo electric organ. Eur J Pharmacol. 2000 Feb 25;390(1-2):7-13. PubMed PMID: 10708701. 4: Tecle H, Barrett SD, Lauffer DJ, Augelli-Szafran C, Brann MR, Callahan MJ, Caprathe BW, Davis RE, Doyle PD, Eubanks D, Lipiniski W, Mirzadegan T, Moos WH, Moreland DW, Nelson CB, Pavia MR, Raby C, Schwarz RD, Spencer CJ, Thomas AJ, Jaen JC. Design and synthesis of m1-selective muscarinic agonists: (R)-(-)-(Z)-1-Azabicyclo[2.2.1]heptan-3-one, O-(3-(3'-methoxyphenyl)-2-propynyl)oxime maleate (CI-1017), a functionally m1-selective muscarinic agonist. J Med Chem. 1998 Jul 2;41(14):2524-36. PubMed PMID: 9651157. 5: Disterhoft JF, Matthew Oh M. Modulation of cholinergic transmission enhances excitability of hippocampal pyramidal neurons and ameliorates learning impairments in aging animals. Neurobiol Learn Mem. 2003 Nov;80(3):223-33. PubMed PMID: 14521865. 6: Lavelle TA, Weinstein MC, Newhouse JP, Munir K, Kuhlthau KA, Prosser LA. Economic burden of childhood autism spectrum disorders. Pediatrics. 2014 Mar;133(3):e520-9. doi: 10.1542/peds.2013-0763. Epub 2014 Feb 10. PubMed PMID: 24515505. 7: Zafar HM, Yang J, Armstrong K, Groeneveld P. Cost Differences After Initial CT Colonography Versus Optical Colonoscopy in the Elderly. Acad Radiol. 2015 Jul;22(7):807-13. doi: 10.1016/j.acra.2015.03.002. Epub 2015 Apr 15. PubMed PMID: 25890873; PubMed Central PMCID: PMC4418202. 8: Bohme TM, Augelli-Szafran CE, Hallak H, Pugsley T, Serpa K, Schwarz RD. Synthesis and pharmacology of benzoxazines as highly selective antagonists at M(4) muscarinic receptors. J Med Chem. 2002 Jul 4;45(14):3094-102. Erratum in: J Med Chem 2002 Oct 10;45(21):4800. PubMed PMID: 12086495. 9: Dijk SN, Francis PT, Stratmann GC, Bowen DM. Cholinomimetics increase glutamate outflow via an action on the corticostriatal pathway: implications for Alzheimer's disease. J Neurochem. 1995 Nov;65(5):2165-9. PubMed PMID: 7595503. 10: Nikolov R. Alzheimer's disease therapy - an update. Drug News Perspect. 1998 May;11(4):248-55. PubMed PMID: 15616667. 1 Lalonde RL, Kowalski KG, Hutmacher MM, Ewy W, Nichols DJ, Milligan PA, Corrigan BW, Lockwood PA, Marshall SA, Benincosa LJ, Tensfeldt TG, Parivar K, Amantea M, Glue P, Koide H, Miller R. Model-based drug development. Clin Pharmacol Ther. 2007 Jul;82(1):21-32. Epub 2007 May 23. Review. PubMed PMID: 17522597. 12: Disterhoft JF, Oh MM. Pharmacological and molecular enhancement of learning in aging and Alzheimer's disease. J Physiol Paris. 2006 Mar-May;99(2-3):180-92. Epub 2006 Feb 3. Review. PubMed PMID: 16458491. 13: Lockwood P, Ewy W, Hermann D, Holford N. Application of clinical trial simulation to compare proof-of-concept study designs for drugs with a slow onset of effect; an example in Alzheimer's disease. Pharm Res. 2006 Sep;23(9):2050-9. Epub 2006 Aug 12. PubMed PMID: 16906456. 14: Bymaster FP, Carter PA, Peters SC, Zhang W, Ward JS, Mitch CH, Calligaro DO, Whitesitt CA, DeLapp N, Shannon HE, Rimvall K, Jeppesen L, Sheardown MJ, Fink-Jensen A, Sauerberg P. Xanomeline compared to other muscarinic agents on stimulation of phosphoinositide hydrolysis in vivo and other cholinomimetic effects. Brain Res. 1998 Jun 8;795(1-2):179-90. PubMed PMID: 9622623.

纯度：≥98%

CAS：161774-09-0