On the statistics of drug-receptor constants for partial agonists.

A linear relationship between equieffective concentrations of agonist in the presence and absence of partial agonist was examined statistically. These experimental concentrations permit the estimation of the apparent dissociation constant Kp with a weighted fit. The form of the weights was proposed theoretically and substantiated by simulated experiments. Constants Kp for (+/-)-p-chloroisoproterenol were estimated from the antagonism by three concentrations of (+/-)-p-chloroisoproterenol of the positive chronotropic effects of (-)-isoproterenol on kitten (Kp = 1.75 X 10(-7) M) and guinea-pig (Kp = 1.84 X 10(-7) M) right atria. The Kp values were similar regardless of the concentrations of (+/-)-p-chloroisoproterenol used; they were also similar to a Kp of 1.95 X 10(-7) M) estimated BY Kaumann and Birnbaumer (J. Biol. Chem. 249: 7874-7885, 1974) for the (+/-)-p-chloroisoproterenol-receptor complex coupled to the adenylyl cyclase in cell-free membrane particles of kitten heart. The proposed statistical procedure appears to be useful for systems with sigmoid log concentration-effect curves in which concentrations of the dependent variable are obtained from interpolation.