Xanomeline

Xanomeline
Systematic (IUPAC) name
3-(4-Hexoxy-1,2,5-thiadiazol-3-yl)-1-methyl-5,6-dihydro-2H-pyridine
Identifiers
CAS Number 131986-45-3
ATC code None
PubChem CID 60809
IUPHAR/BPS 57
ChemSpider 54797
UNII 9ORI6L73CJ YesY
KEGG D06330
ChEMBL CHEMBL21536
Chemical data
Formula C14H23N3OS
Molar mass 281.42 g/mol

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 (Basel, Switzerland) 7 (4): 187–95. PMID 8835881.
  2. ↑ Jakubík J, Michal P, Machová E, Dolezal V (2008). "Importance and prospects for design of selective muscarinic agonists" (PDF). Physiological Research / Academia Scientiarum Bohemoslovaca. 57 Suppl 3: S39–47. 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.
  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 : MN 19 (1-2): 187–93. doi:10.1007/s12031-002-0031-5. PMID 12212779.
  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. 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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