From Wikipedia, the free encyclopedia
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
^ 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 . CS1 maint: multiple names: authors list (link )
^ 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 . {{cite journal }}
: CS1 maint: multiple names: authors list (link )
^ 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 . {{cite journal }}
: CS1 maint: multiple names: authors list (link )
^ 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 . CS1 maint: multiple names: authors list (link )
^ 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 .
^ 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 . {{cite journal }}
: CS1 maint: multiple names: authors list (link )
^ 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 .
^ 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 . {{cite journal }}
: CS1 maint: multiple names: authors list (link )
^ CS1 maint: multiple names: authors list (link )
Template:Nootropics
mAChRs Tooltip Muscarinic acetylcholine receptors
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WIN-2299
Xanomeline
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Precursors (and prodrugs )
nAChRs Tooltip Nicotinic acetylcholine receptors
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RJR-2429
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