CHARACTERIZATION OF THE INTERACTION OF ZAMIFENACIN AT MUSCARINIC RECEPTORS IN-VITRO

The interaction of zamifenacin methoxy-1-(3,4)-methylenedioxyphenethyl )piperidne) at muscarinic receptor subtypes was studied using radiolig and binding and functional techniques, in vitro. In radioligand bindin g studies, zamifenacin acted as a competitive antagonist, with the fol lowing pK(i) values; rat cerebral cortex (M(1)) 7.90 +/- 0.08, myocard ium (M(2)) 7.93 +/- 0.13, submaxillary gland (M(3)) 8.52 +/- 0.04 and rabbit lung (M(4)) 7.78 +/- 0.04. In functional studies zamifenacin ac ted as a surmountable antagonist, exhibiting the following apparent af finity values; canine saphenous vein (putative M(1)) 7.93 +/- 0.09, gu inea-pig left atria (M(2)) 6.60 +/- 0.04, guinea-pig ileum (M(3)) 9.31 +/- 0.06, guinea-pig oesophageal muscularis mucosae (M(3)) 8.84 +/- 0 .04, guinea-pig trachea (M(3)) 8.16 +/- 0.04, and guinea-pig urinary b ladder (M(3)) 7.57 +/- 0.15. Therefore, zamifenacin is selective for m uscarinic M(3) receptors in guinea-pig ileum, oesophageal muscularis m ucosae, trachea and bladder over muscarinic M(2) receptors in atria. T he degree of muscarinic M(3)/M(2) receptor selectivity depends upon th e muscarinic M(3) receptor preparation studied.