Xanomeline
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]
[edit] See also
[edit] 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.
- ^ Jakubík J, Michal P, Machová E, Dolezal V (2008). "Importance and prospects for design of selective muscarinic agonists". Physiological Research / Academia Scientiarum Bohemoslovaca 57 Suppl 3: S39–47. PMID 18481916. http://www.biomed.cas.cz/physiolres/pdf/57%20Suppl%203/57_S39.pdf.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)01252-1.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(09)00033-8.
- ^ 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. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&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. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=18676593.
- ^ 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.
- ^ 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. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=18593778.
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- Agonists: 77-LH-28-1
- AC-42
- AC-260,584
- Aceclidine
- Acetylcholine
- AF30
- AF150(S)
- AF267B
- AFDX-384
- Alvameline
- AQRA-741
- Arecoline
- Bethanechol
- Butyrylcholine
- Carbachol
- CDD-0034
- CDD-0078
- CDD-0097
- CDD-0098
- CDD-0102
- Cevimeline
- cis-Dioxolane
- Ethoxysebacylcholine
- LY-593,039
- L-689,660
- LY-2,033,298
- McNA343
- Methacholine
- Milameline
- Muscarine
- NGX-267
- Ocvimeline
- Oxotremorine
- PD-151,832
- Pilocarpine
- RS86
- Sabcomeline
- SDZ 210-086
- Sebacylcholine
- Suberylcholine
- Talsaclidine
- Tazomeline
- Thiopilocarpine
- Vedaclidine
- VU-0029767
- VU-0090157
- VU-0152099
- VU-0152100
- VU-0238429
- WAY-132,983
- Xanomeline
- YM-796
Antagonists: 3-Quinuclidinyl Benzilate
- 4-DAMP
- Aclidinium Bromide
- Anisodamine
- Anisodine
- Atropine
- Atropine Methonitrate
- Benactyzine
- Benzatropine (Benztropine)
- Benzydamine
- BIBN 99
- Biperiden
- Bornaprine
- CAR-226,086
- CAR-301,060
- CAR-302,196
- CAR-302,282
- CAR-302,368
- CAR-302,537
- CAR-302,668
- CS-27349
- Cyclobenzaprine
- Cyclopentolate
- Darifenacin
- DAU-5884
- Dimethindene
- Dexetimide
- DIBD
- Dicyclomine (Dicycloverine)
- Ditran
- EA-3167
- EA-3443
- EA-3580
- EA-3834
- Etanautine
- Etybenzatropine (Ethylbenztropine)
- Flavoxate
- Himbacine
- HL-031,120
- Ipratropium bromide
- J-104,129
- Hyoscyamine
- Mamba Toxin 3
- Mamba Toxin 7
- Mazaticol
- Mebeverine
- Methoctramine
- Metixene
- N-Ethyl-3-Piperidyl Benzilate
- N-Methyl-3-Piperidyl Benzilate
- Orphenadrine
- Otenzepad
- Oxybutynin
- PBID
- PD-102,807
- PD-0298029
- Phenglutarimide
- Phenyltoloxamine
- Pirenzepine
- Piroheptine
- Procyclidine
- Profenamine
- RU-47,213
- SCH-57,790
- SCH-72,788
- SCH-217,443
- Scopolamine (Hyoscine)
- Solifenacin
- Telenzepine
- Tiotropium bromide
- Tolterodine
- Trihexyphenidyl
- Tripitamine
- Tropatepine
- Tropicamide
- WIN-2299
- Xanomeline
- Zamifenacin; Others: 1st Generation Antihistamines (Brompheniramine
- chlorphenamine
- cyproheptadine
- dimenhydrinate
- diphenhydramine
- doxylamine
- mepyramine/pyrilamine
- phenindamine
- pheniramine
- tripelennamine
- triprolidine, etc)
- Tricyclic Antidepressants (Amitriptyline
- doxepin
- trimipramine, etc)
- Tetracyclic Antidepressants (Amoxapine
- maprotiline, etc)
- Typical Antipsychotics (Chlorpromazine
- thioridazine, etc)
- Atypical Antipsychotics (Clozapine
- olanzapine
- quetiapine, etc)
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- Agonists: 5-HIAA
- A-84,543
- A-366,833
- A-582,941
- A-867,744
- ABT-202
- ABT-418
- ABT-560
- ABT-894
- Acetylcholine
- Altinicline
- Anabasine
- Anatoxin-a
- AR-R17779
- Butyrylcholine
- Carbachol
- Cotinine
- Cytisine
- Decamethonium
- Desformylflustrabromine
- Dianicline
- Dimethylphenylpiperazinium
- Epibatidine
- Epiboxidine
- Ethanol
- Ethoxysebacylcholine
- EVP-4473
- EVP-6124
- Galantamine
- GTS-21
- Ispronicline
- Lobeline
- MEM-63,908 (RG-3487)
- Nicotine
- NS-1738
- PHA-543,613
- PHA-709,829
- PNU-120,596
- PNU-282,987
- Pozanicline
- Rivanicline
- Sazetidine A
- Sebacylcholine
- SIB-1508Y
- SIB-1553A
- SSR-180,711
- Suberylcholine
- TC-1698
- TC-1734
- TC-1827
- TC-2216
- TC-5214
- TC-5619
- TC-6683
- Tebanicline
- Tropisetron
- UB-165
- Varenicline
- WAY-317,538
- XY-4083
Antagonists: 18-Methoxycoronaridine
- α-Bungarotoxin
- α-Conotoxin
- Alcuronium
- Amantadine
- Anatruxonium
- Atracurium
- Bupropion (Amfebutamone)
- Chandonium
- Chlorisondamine
- Cisatracurium
- Coclaurine
- Coronaridine
- Dacuronium
- Decamethonium
- Dextromethorphan
- Dextropropoxyphene
- Dextrorphan
- Diadonium
- DHβE
- Dimethyltubocurarine (Metocurine)
- Dipyrandium
- Dizocilpine (MK-801)
- Doxacurium
- Duador
- Esketamine
- Fazadinium
- Gallamine
- Hexafluronium
- Hexamethonium (Benzohexonium)
- Ibogaine
- Isoflurane
- Ketamine
- Kynurenic acid
- Laudexium (Laudolissin)
- Levacetylmethadol
- Malouetine
- Mecamylamine
- Memantine
- Methadone
- Methorphan (Racemethorphan)
- Methyllycaconitine
- Metocurine
- Mivacurium
- Morphanol (Racemorphanol)
- Neramexane
- Nitrous Oxide
- Pancuronium
- Pempidine
- Pentamine
- Pentolinium
- Phencyclidine
- Pipecuronium
- Radafaxine
- Rapacuronium
- Rocuronium
- Surugatoxin
- Suxamethonium (Succinylcholine)
- Thiocolchicoside
- Toxiferine
- Trimethaphan
- Tropeinium
- Tubocurarine
- Vecuronium
- Xenon
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- Cymserine * Many of the acetylcholinesterase inhibitors listed above act as butyrylcholinesterase inhibitors.
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