A simplified empirical approach to evaluate the dissociation constant of afull agonist by the irreversible receptor inactivation method

The estimation of the dissociation constant (Ka) of full agonists represent s an essential tool for the classification of drugs and drug receptors, in functional pharmacology. The evaluation of the Ka was a problem until the d evelopment of the Furchgott's method (irreversible partial receptor inactiv ation method), which surely represents the most used analysis for the evalu ation of the agonist Ka in experimental protocols on isolated tissues. The Furchgott's method can furnish a reliable estimation of the Ka, but it requ ires a relatively complicated manipulation of experimental data. In this ar ticle, an alternative approach for the evaluation of the Ka is proposed, on the basis of empirical considerations. This method, also based on the part ial alkylation of a fraction of receptors, needs only the knowledge of the location parameters of the concentration-response curves and the applicatio n of a very simple equation, without any complicated intermediate interpola tion of the experimental data. (C) 1999 Elsevier Science Inc.