EC50 and Spare Receptors

In relation to drug concentration and responses, what is the EC50 and what are spare receptors?

• EC50 is the concentration at which an agonist produces half its maximal effect. I.e. the potency of the drug. The smaller the EC50, the greater the drug potency
• The concentration of an agonist producing a maximum response may not result in occupancy of all the receptors. These receptors are said to be “spare”.
• These spare receptors can either be in number i.e. there are an excess number of receptors, not all are occupied. Or temporal: the effect of activation of the receptor may be longer than the duration of drug-receptor interaction. I.e. may be longer than the time spent bound to the receptor. This results in “spare receptors”

Draw a dose response curve for an irreversible antagonist as the spare receptors become occupied.

• The curves shift to the right as the spare receptors become occupied at increasing doses of antagonist.
• Curve A represents pure agonist.
• Curve B is agonist with a low dose antagonist. It still produces a maximal effect as spare receptors are still available.
• Curve C shows the largest concentration of antagonist where the available receptors are no longer spare, instead, they are just sufficient to mediate an undiminished maximal response, but with higher doses of agonist.
• Then as the concentration of antagonist increases maximal effect is diminished as represented by curve D and E.