Add time:08/05/2019         Source:sciencedirect.com

The interaction of zamifenacin (cas 127263-13-2) ((3R)-(+)-diphenylmethoxy-1-(3,4)-methylenedioxyphenethyl)piperidine) at muscarinic receptor subtypes was studied using radioligand binding and functional techniques, in vitro. In radioligand binding studies, zamifenacin acted as a competitive antagonist, with the following pKi values; rat cerebral cortex (M1) 7.90 ± 0.08, myocardium (M2) 7.93 ± 0.13, submaxillary gland (M3) 8.52 ± 0.01 and rabbit lung (M4) 7.78 ± 0.04. In functional studies zamifenacin acted as a surmountable antagonist, exhibiting the following apparent affinity values; canine saphenous vein (putative M1) 7.93 ± 0.09, guinea-pig left atria (M2) 6.60 ± 0.04, guinea-pig ileum (M3) 9.31 ± 0.06, guinea-pig oesophageal muscularis mucosae (M3) 8.84 ± 0.04, guinea-pig trachea (M3) 8.16 ± 0.04, and guinea-pig urinary bladder (M3) 7.57 ± 0.15. Therefore, zamifenacin is selective for muscarinic M3 receptors in guinea-pig ileum, oesophageal muscularis mucosae, trachea and bladder over muscarinic M2 receptors in atria. The degree of muscarinic M3M2 receptor selectivity depends upon the muscarinic M3 receptor preparation studied.

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