SEARCH FOR SELECTIVE ANTAGONISTS AT ALPHA(1)-ADRENORECEPTORS - NEUTRAL OR NEGATIVE ANTAGONISM

In this article the use of competitive antagonists as tools in recepto r characterization and classification is discussed. It is pointed out that caution is required in receptor characterization because negative antagonism (inverse agonism) rather than neutral antagonism could pla y a relevant role. This implies that antagonists should be evaluated n ot only with regard to their affinity, but also with regard to their a bility to affect the equilibrium between the two receptor states, name ly active and inactive states. Since affinity and efficacy of a negati ve antagonist are system dependent the use of negative antagonists as competitive antagonists in receptor characterization may give rise to false differences in receptor subtypes. Finally, this article summariz es recent developments in the design of new alpha(1)-adrenoreceptor an tagonists which are structurally related to prazosin or WB 4101. (C) 1 998 Elsevier Science S.A. All rights reserved.