QUANTITATIVE ESTIMATION OF POTENTIATION AND ANTAGONISM BY DOSE RATIOSCORRECTED FOR SLOPES OF DOSE-RESPONSE CURVES DEVIATING FROM ONE

A shift of dose-response curves of a receptor agonist A by a receptor antagonist B to the right is frequently expressed or quantitated by ca lculating the dose ratio (DR) from the ED(50) values obtained in the a bsence and presence of B. A comparison of ED(50) values or a DR is als o used in a more general way to express the effects of other antagonis ts or of potentiators. For this situation, where B is not competing wi th A for a binding site, slope-values may often deviate from one. Beca use the slope of shifted dose-response curves (deviating from one) aff ects the magnitude of enhancement or diminution at a given DR, we have to take it into account. For example, the same changes in effects are associated with DR = 10 at curves with slope = 1, but with DR = 2.15 in case of slope = 3. Enhancement and diminution expressed by dose rat ios is more or less underestimated in case of curves with slope >1. We therefore propose to quantitate potentiation and antagonism by a corr ected DR (DR(corr)), which can simply be calculated from the uncorrect ed DR at a given slope. Consequently, a DR(corr) reflects a true measu re of enhancement or diminution for curves with slope = 1, equivalent to that which would have been observed for curves with slope = 1. The practical value of this modification is exemplified and illustrated by analysis of experimental data.