Question

A pharmaceutical company is developing 3 new drugs that bind to the same receptor as nicotine and acetylcholine (ACh). They perform a series of experiments to determine the concentration-response relationship for each new drug.

All drugs showed a sigmoidal concentration-response curve when plotted on a semi-logarithmic scale.

Their data shows that Drug A has an EC₅₀ of 100 nM and a maximum effect of 99%. Drug B has an EC₅₀ of 15 nM and a maximum effect of 95%. Drug C has an EC₅₀ of 85 nM and a maximum effect of 45%.

a) What type of receptor protein do these 3 drugs bind to? (1 mark)

b) What is the timescale between binding of an agonist drug to this receptor and the cellular response? (1 mark)

c) Which drug (A, B or C) is the least potent drug? (1 mark)

d) What type of drug is Drug C? Briefly justify your answer.

Answer 1

A) These 3 drugs bind to the nicotinic acetylcholine (Ach) ionotropic receptor. ionotropic receptors are ligand-gated ion channels that allow non-specific cations to pass through, bringing about changes in membrane current.

B) These receptors are relatively fast and bring about an effect on a millisecond timescale

C) The EC50 is the concentration of the drug that gives 'half-maximal response'. The lower the EC50, the more potent the drug. However, between these 3 drugs, it is complex because the maximal response by drug A and drug C is very different. So, even though the EC50 of drug C is only 85nM as compared to that of drug A (100nM), since the maximal response it only 45%, drug C is the least potent drug.

D) Drug C is a partial agonist. A partial agonist is a drug that binds to the receptor and gives sub-maximal response when compared to the endogenous (or full) agonist. Since drug C has a maximal response of only 45%, it is a partial agonist.