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 analysis are the most widely used among the reliable different methods actually available, for the determination of the dissociation constant of partial agonists. However, they need the application of relatively complicated procedures of manipulation and interpolation of raw data. On the basis of empirical assumptions, this article proposes a new approach, which probably can be considered the simplest method to determine the dissociation constant of a partial agonist, because of the rapid experimental protocol and the easy calculation 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 dissociation 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 experimentally studied partial agonists, showed a high level of accuracy, when compared with the classical Waud's analysis.
Calderone
V
V
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università degli Studi di Pisa, Italy. calderone@farm.unipi.it
Martinotti
E
E
D000316:Adrenergic alpha-Agonists / Q000737:chemistry*; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D003198:Computer Simulation; D003625:Data Collection; D004305:Dose-Response Relationship, Drug; D008956:Models, Chemical; D011817:Rabbits; D051381:Rats
D000316:Adrenergic alpha-Agonists