Intrinsic activity and EC50: The simplest tools for the evaluation of the dissociation constant of a partial agonist

In functional pharmacology, the Furchgott's analysis and the Waud's analysi s are the most widely used among the reliable different methods actually av ailable, for the determination of the dissociation constant of partial agon ists. However, they need the application of relatively complicated procedur es of manipulation and interpolation of raw data. On the basis of empirical assumptions, this article proposes a new approach, which probably can be c onsidered the simplest method to determine the dissociation constant of a p artial agonist, because of the rapid experimental protocol and the easy cal culation procedure. Computer-generated concentration-response curves (CRC) for hypothesised partial agonists were analysed by the widely known Waud's analysis and by this new approach. Furthermore, this new analysis was also used to evaluate experimental data from literature, relative to the dissoci ation constants of alpha-adrenoceptor partial agonists, recorded in rabbit and rat aortae and calculated by the Waud's method. The results obtained by the new approach, both for the computer-generated and for the experimental ly studied partial agonists, showed a high level of accuracy, when compared with the classical Waud's analysis. (C) 1999 Elsevier Science Inc.