Table 2

Antagonistic action of W84 at M1/M4-like receptors in rabbit vas deferens (RDV), at M2 receptors in guinea-pig atria (GPA), and at M3 receptors in guinea-pig ileum (GPI)

SubtypeAgonistCooperativity modelCompetitive model
KAαKB (Constrained plot)Slope
nm nm
M1/M4(RDV)McNN.D.N.D.759  ± 671.15  ± 0.06
M2(GPA)Oxo137  ± 28311  ± 16N.D.N.D.
APE180  ± 11495  ± 108N.D.N.D.
M3(GPI)APEN.D.N.D.4,370  ± 8201.21  ± 0.23

The equilibrium dissociation constants K A and cooperativity factors α for the allosteric interaction of W84 with oxotremorine (Oxo) and APE, respectively, at M2 receptors were derived from an analysis based on the cooperativity model. The interaction of W84 with 4-Cl-McN-A-343 (McN) at M1/M4and APE at M3 receptors was analysed according to Arunlakshana and Schild (1959). Because the slopes of the Schild plots did not differ significantly (p > 0.05, ttest) from unity, K B values were estimated by fitting to the data the best straight line with a slope of 1.00. Listed are mean values ± standard error of three to eight experiments performed in separate preparations.

    • N.D., not determined.