What effect does the addition of an irreversible antagonist have on a dose-response curve?

What effect does the addition of an irreversible antagonist have on a dose-response curve?

• A. Shifts the curve to the left, increasing potency with no change in maximal response
• B. Shifts the curve progressively right and downward, decreasing maximal response; cannot be reversed
• C. Causes the curve to become steeper without shifting
• D. Has no effect on the curve

Answer: (B)

An irreversible antagonist acts as a noncompetitive blocker, reducing the number of functional receptors available for activation. Because fewer receptors can respond, the maximal effect the agonist can produce is lowered (Emax) and you need more agonist to achieve the same effect (EC50 increases), so the curve shifts to the right and downward. This reduction in maximal response cannot be overcome by simply increasing the agonist concentration in the same system, since blocked receptors can’t signal. If receptor synthesis or system recovery occurs later, some reversal is possible, but acutely the effect is not reversible.

An irreversible antagonist acts as a noncompetitive blocker, reducing the number of functional receptors available for activation. Because fewer receptors can respond, the maximal effect the agonist can produce is lowered (Emax) and you need more agonist to achieve the same effect (EC50 increases), so the curve shifts to the right and downward. This reduction in maximal response cannot be overcome by simply increasing the agonist concentration in the same system, since blocked receptors can’t signal. If receptor synthesis or system recovery occurs later, some reversal is possible, but acutely the effect is not reversible.