Question

Drugs A, B, and C are Dopamine Receptor Agonists used to treat Parkinson’s disease.  Drug A has an EC₅₀of 30 mg/mL, Drug B has an EC₅₀of 20 µg/mL, and Drug C has an EC₅₀of 40 g/mL.  Drug C is 50% less efficacious than Drugs A or B.  Graph these drugs on a semi-log graded dose-response curve (all on one graph and label the axis).  Can you determine the K_dof each of these drugs from the data (tell me why or why not too: HINT-look up the receptor type in your book)?  Which drug(s) have the highest potency and which has the highest efficacy; put the drugs in order for potency (high to low) and efficacy (high to low).  What is the most ideal drug; put the drugs in order of the most ideal to least ideal drug (defend your answer too)?  Tell whether each of these drugs are Full or Partial Agonists. (4.5 points)

Answer 1

The drugs used were dopamine receptor agonists for the treatment of parkinson’s disease. Dopamine receptors are G-protein coupled receptors. The drugs A, B, and C have EC 50 values of 30mg/ml, 20µg/ml, and 40g/ml.

EC50 is the concentration of the drug which results in the 50 percent of the maximal effect (E_max).

The graded dose-response curve needs to be drawn for all the 3 drugs in one graph. The graded response is when there is an increasing magnitude of response with the increasing dose.

Kd is the dissociation constant. The dissociation constant is inversely proportional to binding affinity of drug to the receptor. So, when there is low dissociation constant the affinity will be high and high association constant. Likewise when there is high dissociation constant there will be low binding affinity and low association constant.

The dissociation constant can’t be calculated from the given data as for the calculation of Kd we also need the protein concentration. The kd is sum of the concentrations of drug and protein or receptor divided by the concentration of receptor-drug complex.

Relative potency is when 2 agonists with equal efficacy, a small dose of one agonist is required to achieve maximal effect. The potency is inversely proportional to EC50 of drug.

Relative efficacy is when the maximal effect of one agonist is greater than the other. Irrespective of drug concentration.

Potency: drug B, drug A, and drug C (decreasing order of potency)

Efficacy: Drug C, drug A, and drug B (decreasing order of efficacy)

The agonist drug which binds to receptor and activates but have partial efficacy are partial agonists while the full agonists activates the receptor completely after binding and have full efficacy with the maximal effect.

A drug with more efficacy is important than the ones that are potent and have less efficacy.

So, according to me from the graph drug c is the ideal drug with respect to the efficacy as it elicits the maximum drug response.

Drug B is a full agonist while drug A and C were partial agonists