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Chemical Compound Review

Lumeron     3-(4-hexoxy-1,2,5-thiadiazol- 3-yl)-1...

Synonyms: XANOMELINE, Hexyloxy-TZTP, CHEMBL21536, SureCN121046, AG-D-64976, ...
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Disease relevance of C11767


Psychiatry related information on C11767


High impact information on C11767


Chemical compound and disease context of C11767


Biological context of C11767


Anatomical context of C11767


Associations of C11767 with other chemical compounds


Gene context of C11767

  • These compounds, however, were more potent in the analgesia tests than the selective M1 agonists xanomeline and hexylthio-TZTP [19].
  • Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors [14].
  • Similar studies on human cloned receptors confirmed that xanomeline is an agonist at human cloned 5-HT1A and 5-HT1B receptors [14].
  • In studies using the fluorescent cytoplasmic Ca2+ indicator FLUO-3AM, xanomeline induced an increase in cytoplasmic Ca2+ concentration in SH-SY5Y cells expressing recombinant human 5-HT2C receptors [14].
  • The results of the current study suggest that elucidation of the mechanism or mechanisms of interaction of xanomeline with the M1 mAChR is particularly important in relation to the potential therapeutic use of this agent in the treatment of Alzheimer's disease [11].

Analytical, diagnostic and therapeutic context of C11767

  • 1H-MRS spectra were collected at baseline and after treatment discontinuation for 12 patients, two taking placebo and 10 taking xanomeline at a dose of 25 mg t.i.d. (N = 4), 50 mg t.i.d. (N = 3), or 75 mg t.i.d. (N = 3) [5].
  • METHODS: The effect of xanomeline on extracellular levels of monoamines in brain regions was determined using a microdialysis technique, and changes in expression of the immediate early genes c-fos and zif/268 in brain regions were evaluated using in situ hybridization histochemistry [10].
  • The antipsychotic-like effects of xanomeline in the animal models used here suggest that it may be a useful treatment for psychosis [20].
  • A reversed-phase high-performance liquid chromatographic assay (HPLC) was utilized for monitoring xanomeline (LY246708/NNC 11-0232) and a metabolite, desmethylxanomeline, in human plasma [21].
  • Determination of xanomeline (LY246708 tartrate), an investigational agent for the treatment of Alzheimer's disease, in rat and monkey plasma by capillary gas chromatography with nitrogen-phosphorus detection [22].


  1. Effects of central muscarinic-1 receptor stimulation on blood pressure regulation. Medina, A., Bodick, N., Goldberger, A.L., Mac Mahon, M., Lipsitz, L.A. Hypertension (1997) [Pubmed]
  2. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys. Andersen, M.B., Fink-Jensen, A., Peacock, L., Gerlach, J., Bymaster, F., Lundbaek, J.A., Werge, T. Neuropsychopharmacology (2003) [Pubmed]
  3. Low-affinity M(2) receptor binding state mediates mouse atrial bradycardia: comparative effects of carbamylcholine and the M(1) receptor agonists sabcomeline and xanomeline. Stengel, P.W., Cohen, M.L. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  4. Xanomeline, an M(1)/M(4) preferring muscarinic cholinergic receptor agonist, produces antipsychotic-like activity in rats and mice. Shannon, H.E., Rasmussen, K., Bymaster, F.P., Hart, J.C., Peters, S.C., Swedberg, M.D., Jeppesen, L., Sheardown, M.J., Sauerberg, P., Fink-Jensen, A. Schizophr. Res. (2000) [Pubmed]
  5. Brain proton magnetic resonance spectroscopy (1H-MRS) in Alzheimer's disease: changes after treatment with xanomeline, an M1 selective cholinergic agonist. Satlin, A., Bodick, N., Offen, W.W., Renshaw, P.F. The American journal of psychiatry. (1997) [Pubmed]
  6. Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Bodick, N.C., Offen, W.W., Levey, A.I., Cutler, N.R., Gauthier, S.G., Satlin, A., Shannon, H.E., Tollefson, G.D., Rasmussen, K., Bymaster, F.P., Hurley, D.J., Potter, W.Z., Paul, S.M. Arch. Neurol. (1997) [Pubmed]
  7. Efficacy of xanomeline in Alzheimer disease: cognitive improvement measured using the Computerized Neuropsychological Test Battery (CNTB). Veroff, A.E., Bodick, N.C., Offen, W.W., Sramek, J.J., Cutler, N.R. Alzheimer disease and associated disorders. (1998) [Pubmed]
  8. Xanomeline and the antipsychotic potential of muscarinic receptor subtype selective agonists. Mirza, N.R., Peters, D., Sparks, R.G. CNS drug reviews. (2003) [Pubmed]
  9. Differences in kinetics of xanomeline binding and selectivity of activation of G proteins at M(1) and M(2) muscarinic acetylcholine receptors. Jakubík, J., El-Fakahany, E.E., Dolezal, V. Mol. Pharmacol. (2006) [Pubmed]
  10. The muscarinic agonist xanomeline increases monoamine release and immediate early gene expression in the rat prefrontal cortex. Perry, K.W., Nisenbaum, L.K., George, C.A., Shannon, H.E., Felder, C.C., Bymaster, F.P. Biol. Psychiatry (2001) [Pubmed]
  11. On the unique binding and activating properties of xanomeline at the M1 muscarinic acetylcholine receptor. Christopoulos, A., Pierce, T.L., Sorman, J.L., El-Fakahany, E.E. Mol. Pharmacol. (1998) [Pubmed]
  12. The safety and tolerance of xanomeline tartrate in patients with Alzheimer's disease. Sramek, J.J., Hurley, D.J., Wardle, T.S., Satterwhite, J.H., Hourani, J., Dies, F., Cutler, N.R. Journal of clinical pharmacology. (1995) [Pubmed]
  13. Persistent binding and functional antagonism by xanomeline at the muscarinic M5 receptor. Grant, M.K., El-Fakahany, E.E. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  14. Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. Watson, J., Brough, S., Coldwell, M.C., Gager, T., Ho, M., Hunter, A.J., Jerman, J., Middlemiss, D.N., Riley, G.J., Brown, A.M. Br. J. Pharmacol. (1998) [Pubmed]
  15. Xanomeline: a novel muscarinic receptor agonist with functional selectivity for M1 receptors. Shannon, H.E., Bymaster, F.P., Calligaro, D.O., Greenwood, B., Mitch, C.H., Sawyer, B.D., Ward, J.S., Wong, D.T., Olesen, P.H., Sheardown, M.J. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  16. Pharmacological analysis of the novel mode of interaction between xanomeline and the M1 muscarinic acetylcholine receptor. Christopoulos, A., Parsons, A.M., El-Fakahany, E.E. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  17. Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry. Wood, M.D., Murkitt, K.L., Ho, M., Watson, J.M., Brown, F., Hunter, A.J., Middlemiss, D.N. Br. J. Pharmacol. (1999) [Pubmed]
  18. Neurochemical effects of the M1 muscarinic agonist xanomeline (LY246708/NNC11-0232). Bymaster, F.P., Wong, D.T., Mitch, C.H., Ward, J.S., Calligaro, D.O., Schoepp, D.D., Shannon, H.E., Sheardown, M.J., Olesen, P.H., Suzdak, P.D. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  19. M1 receptor agonist activity is not a requirement for muscarinic antinociception. Sheardown, M.J., Shannon, H.E., Swedberg, M.D., Suzdak, P.D., Bymaster, F.P., Olesen, P.H., Mitch, C.H., Ward, J.S., Sauerberg, P. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  20. The muscarinic receptor agonist xanomeline has an antipsychotic-like profile in the rat. Stanhope, K.J., Mirza, N.R., Bickerdike, M.J., Bright, J.L., Harrington, N.R., Hesselink, M.B., Kennett, G.A., Lightowler, S., Sheardown, M.J., Syed, R., Upton, R.L., Wadsworth, G., Weiss, S.M., Wyatt, A. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  21. High-performance liquid chromatographic assay for xanomeline, a specific M-1 agonist, and its metabolite in human plasma. Kasper, S.C., Bonate, P.L., DeLong, A.F. J. Chromatogr. B, Biomed. Appl. (1995) [Pubmed]
  22. Determination of xanomeline (LY246708 tartrate), an investigational agent for the treatment of Alzheimer's disease, in rat and monkey plasma by capillary gas chromatography with nitrogen-phosphorus detection. Brown, T.J., Shipley, L.A. J. Chromatogr. B, Biomed. Appl. (1995) [Pubmed]
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