The properties of the ternary complex model (TCM) of drug action at G protein-coupled receptors (GPCRs) were examined, using theoretical computer simulations, with regard to the predicted effects of the presence of a fixed concentration of one agonist on the competition binding profile of another. Subsequently, the binding properties of the full muscarinic acetylcholine receptor (mAChR) agonists acetylcholine (ACh) and carbachol (CCh), and the partial agonists pilocarpine and McN-A-343, were investigated in competition experiments against [(3)H]N-methylscopolamine using homogenate preparations from Chinese hamster ovary cells, stably expressing the human M(1) or M(2) mAChR. At the M(2) mAChR, all agonists displayed biphasic binding curves and were readily modulated by the non-hydrolyzable GTP analogue, Gpp(NH)p, in accordance with previously established experimental observations. In contrast, agonist binding at the M(1) mAChR showed no significant change in the presence of Gpp(NH)p, even in the case of a full agonist. This phenomenon precludes using the "GTP-shift" to assess agonist efficacy at the M(1) mAChR. When the ACh competition curves were reconstructed in the presence of graded concentrations of either a full or a partial agonist, a significant redistribution of the fraction of the high-affinity state recognized by ACh was observed. However, when the procedure was repeated using the antagonist, atropine, no significant effect on the fraction of either the high or low affinity ACh binding components at the mAChR was observed. Taken together, these results indicate that changes in the profile of full agonist binding isotherms, when constructed in the presence of a partial agonist, may be more sensitive indicators of partial agonist efficacy than regular assays that directly measure partial agonist binding.