Xanomeline

Xanomeline
Clinical data
ATC code
  • None
Identifiers
IUPAC name
  • 3-(4-Hexoxy-1,2,5-thiadiazol-3-yl)-1-methyl-5,6-dihydro-2H-pyridine
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.208.938
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Chemical and physical data
FormulaC14H23N3OS
Molar mass281.42 g·mol−1
3D model (JSmol)
SMILES
  • CCCCCCOC1=NSN=C1C2=CCCN(C2)C

Xanomeline (LY-246,708; Lumeron, Memcor) is a muscarinic acetylcholine receptor agonist with reasonable selectivity for the M1 and M4 subtypes,[1][2][3][4] though it is also known to act as a M5 receptor antagonist.[5] It has been studied for the treatment of both Alzheimer's disease and schizophrenia, particularly the cognitive and negative symptoms,[6] although gastrointestinal side effects led to a high drop-out rate in clinical trials.[7][8] Despite this, xanomeline has been shown to have reasonable efficacy for the treatment of schizophrenia symptoms, and one recent human study found robust improvements in verbal learning and short-term memory associated with xanomeline treatment.[9]

See also

References

  1. ↑ Farde L, Suhara T, Halldin C, et al. (1996). "PET study of the M1-agonists [11C]xanomeline and [11C]butylthio-TZTP in monkey and man". Dementia. 7 (4): 187–95. doi:10.1159/000106877. PMID 8835881.
  2. ↑ Jakubík J, Michal P, Machová E, Dolezal V (2008). "Importance and prospects for design of selective muscarinic agonists" (PDF). Physiological Research. 57 Suppl 3: S39–47. doi:10.33549/physiolres.931449. PMID 18481916.
  3. ↑ Woolley ML, Carter HJ, Gartlon JE, Watson JM, Dawson LA (January 2009). "Attenuation of amphetamine-induced activity by the non-selective muscarinic receptor agonist, xanomeline, is absent in muscarinic M4 receptor knockout mice and attenuated in muscarinic M1 receptor knockout mice". European Journal of Pharmacology. 603 (1–3): 147–9. doi:10.1016/j.ejphar.2008.12.020. PMID 19111716.
  4. ↑ Heinrich JN, Butera JA, Carrick T, et al. (March 2009). "Pharmacological comparison of muscarinic ligands: historical versus more recent muscarinic M1-preferring receptor agonists". European Journal of Pharmacology. 605 (1–3): 53–6. doi:10.1016/j.ejphar.2008.12.044. PMID 19168056.
  5. ↑ Grant MK, El-Fakahany EE (October 2005). "Persistent binding and functional antagonism by xanomeline at the muscarinic M5 receptor". The Journal of Pharmacology and Experimental Therapeutics. 315 (1): 313–9. doi:10.1124/jpet.105.090134. PMID 16002459. S2CID 11016091.
  6. ↑ Lieberman JA, Javitch JA, Moore H (August 2008). "Cholinergic agonists as novel treatments for schizophrenia: the promise of rational drug development for psychiatry". The American Journal of Psychiatry. 165 (8): 931–6. doi:10.1176/appi.ajp.2008.08050769. PMID 18676593.
  7. ↑ Messer WS (2002). "The utility of muscarinic agonists in the treatment of Alzheimer's disease". Journal of Molecular Neuroscience. 19 (1–2): 187–93. doi:10.1007/s12031-002-0031-5. PMID 12212779. S2CID 1745935.
  8. ↑ Mirza NR, Peters D, Sparks RG (2003). "Xanomeline and the antipsychotic potential of muscarinic receptor subtype selective agonists". CNS Drug Reviews. 9 (2): 159–86. doi:10.1111/j.1527-3458.2003.tb00247.x. PMC 6741650. PMID 12847557.
  9. ↑ Shekhar A, Potter WZ, Lightfoot J, et al. (August 2008). "Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia". The American Journal of Psychiatry. 165 (8): 1033–9. doi:10.1176/appi.ajp.2008.06091591. PMID 18593778.
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