PT  - JOURNAL ARTICLE
AU  - Frederick J. Ehlert
AU  - Michael T. Griffin
AU  - Gregory W. Sawyer
AU  - Regina Bailon
TI  - A Simple Method for Estimation of Agonist Activity at Receptor Subtypes: Comparison of Native and Cloned M<sub>3</sub> Muscarinic Receptors in Guinea Pig Ileum and Transfected Cells
DP  - 1999 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 981--992
VI  - 289
IP  - 2
4099  - http://jpet.aspetjournals.org/content/289/2/981.short
4100  - http://jpet.aspetjournals.org/content/289/2/981.full
SO  - J Pharmacol Exp Ther1999 May 01; 289
AB  - We describe a simple method for calculating the pharmacological activity of an agonist (A) relative to a standard agonist (S) using only the concentration-response curves of the two agonists. In most situations, we show that the product of the ratios of maximal responses (E max − A/E max − S) and potencies (EC50 − S/EC50 − A) is equivalent to the product of the affinity and intrinsic efficacy of A expressed relative to that of S. We refer to this term as the IRA value of A. In a cooperative system where the concentration-response curve of the standard agonist is steep and that of the test agonist is flatter with a lower maximal response, the simple calculation of IRA described above underestimates agonist activity; however, we also describe a means of correcting the IRA in this situation. We have validated our analysis with modeling techniques and have shown experimentally that the IRA values of muscarinic agonists for stimulating contractions in the guinea pig ileum (M3 response) are in excellent agreement with those measured in the phosphoinositide assay on Chinese hamster ovary cells expressing the M3 muscarinic receptor. The American Society for Pharmacology and Experimental Therapeutics