Computer-assisted analysis of complex concentration-response data

The analysis of concentration-response data generally relies on graphic techniques to gain estimates of the EC50, maximum response, and Hill coefficient. This type of analysis may be adequate if the drug-mediated response follows the simple mass action law; however, if the drug produces a complex concentration-response relationship through multiple receptor activation this type of analysis can give misleading information regarding the potency and actions of the particular agonist being tested. In addition, graphic analytical techniques can mask potentially useful information. There are, however, many computer programs currently available that can adequately analyze complex concentration-response data by use of weighted nonlinear curve-fitting techniques. The present paper reports on the use of some of these programs (e.g., FUNFIT and LIGAND) and how they might be used to analyze results obtained from experiments where multiple receptor activation occurs. The use of these programs gives more accurate estimates of the required constants and, in addition, can provide useful information regarding the process that produces the complex data.