Xanomeline oxalate Muscarinic receptor agonist

Xanomeline oxalate is a novel agonist of muscarinic receptor with the pKi values of 7.1±0.1, 6.9±0.1, 7.4±0.1, 7.7±0.1 and 7.4±0.2 for hM1, hM2, hM3, hM4 and hM5, respectively. [1].

Xanomeline oxalate has been reported to have the highest affinity for [3H]oxotremorine-M cortical and [3H]pirenzepine hippocampal labeled muscarinic receptors（2±0.5nM and 5±1nM, respectively）. In addition, Xanomeline oxalate has been revealed to produce a concentration-dependent inhibition of electrically stimulated twitch response in isolated rabbit vas deferens with the IC50 value of 0.006nM. Furthermore, Xanomeline oxalate has also been noted to produce the carbachol-stimulated PI hydrolysis with the IC50 values of 0.004±0.001μM, 21±4μM and 0.2±0.08μM in CHO-K1 cell, BHK cell and A9L cell, respectively. Besides, Xanomeline oxalate has been reported to reduce the force of contraction of guinea pig isolated atria with an IC50 value of ~3μM and produce a concentration-dependent contractile response in the guinea pig ileum with an IC50 value of 9nM [2].

References:
[1]Watson J1, Brough S, Coldwell MC, Gager T, Ho M, Hunter AJ, Jerman J, Middlemiss DN, Riley GJ, Brown AM. Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. Br J Pharmacol. 1998 Dec;125(7):1413-20.
[2]Shannon HE1, Bymaster FP, Calligaro DO, Greenwood B, Mitch CH, Sawyer BD, Ward JS, Wong DT, Olesen PH, Sheardown MJ, et al. Xanomeline: a novel muscarinic receptor agonist with functional selectivity for M1 receptors. J Pharmacol Exp Ther. 1994 Apr;269(1):271-81.

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