How can we distinguish between non-competitive and irreversible antagonism?
In functional assays of non-competitive antagonists, depression of the maximal response of agonist dose-response curves, and in some cases, rightward shifts, is produced.[19] The rightward shift will occur as a result of a receptor reserve[10] and inhibition of the agonist response will only occur when this reserve is depleted. Irreversible antagonists covalently bind to the receptor target and generally cannot be removed; inactivating the receptor for the duration of the antagonist effects is determined by the rate of receptor turnover, the rate of synthesis of new receptors. Inactivation of receptors normally results in a depression of the maximal response of agonist dose-response curves and a right shift in the curve occurs where there is a receptor reserve similar to non-competitive antagonists. A washout step in the assay will usually distinguish between non-competitive and irreversible antagonist drugs as effects of non-competitive antagonists are reversible and activity of agoni
