Concepts of Pharmaceutical ScienceProblem 4. Analysis of antagonist potency in tissue (Schild analysis).Below are the results of stimulating an isolated rat ileum (part of the small intestine) with an agonist. The agonist’s molar concentrations are presented in the leftmost (first) column (Example 3E-07 = 3×10-7 M = 300 nM). The normalized control responses to the agonist are presented in the second column as a percentage of the maximum muscle contraction. These measurements are repeated in the presence of an antagonist at varying concentrations. The molar concentration of the antagonist is placed at the top of each subsequent column going to the right and the responses of the tissue are shown below.For AntagFor Antag -9MFor Antag = 2×10-8MFor Antag=2×10-7MAgonist (M)0.00398.6788.220.00199.5696.120.000599.1392.520.000398.5588.1342.830.000199.6095.7919.980.0000599.2191.9111.100.0000398.6887.2142.616.970.0000196.1519.842.440.00000592.5911.010.00000388.2440.546.910.00000118.522.425E-0710.203.00E-0742.866.381.00E-0720.002.225.00E-0811.113.00E-086.981.00E-082.44The experiment involves taking smooth muscle in a bath connected to a force transducer. Full activation with agonist gives a 10 gm contraction with maximum agonist and no antagonist. Varying doses of agonist are given in the presence or absence of 3 doses of antagonist. Some data is missing. The data is recorded as % of maximum response:Questions:Is the antagonist a competitive or noncompetitive antagonist? Justify your answer by showing a plot.Define pA2 in your own words.Calculate pA2 of the antagonist. (Hint: To calculate pA2 you need to compare equivalent responses. What plot can you use to linearize the responses so you can compare equivalent responses? Show your linearized results and how you used them to calculate pA2) Convert pA2 to a concentration.Why do you need to compare equivalent responses? Why is this analysis useful? Give two examples
