Binding, Affinity and Agonists

Question 1

Describe what a ligand?

Answer 1

Drugs that bind to receptors

Question 2

Describe what an agonist is?

Answer 2

Bind to activate receptors and have efficacy to invoke responses

Question 3

Describe what an antagonist is?

Answer 3

Bind to activate receptors and have zero efficacy to block agonists and and do not activate receptors

Question 4

Describe what affinity means in terms of ligands and receptors?

Answer 4

How well a ligand binds to a receptor

Question 5

Describe what efficacy means?

Answer 5

The ability of a drug to ACTIVATE a receptor and cause a RESPONSE

Question 6

Describe what selectivity and specificity means in terms of ligand and receptors?

Answer 6

1. Ability for the ligand to have binding site specificity

2. Property of receptor to only bind certain types of molecules

Question 7

Describe what potency means in terms of the agonist?

Answer 7

1. The measure of the amount of drug required to evoke a given response
2. It’s the interaction of affinity and efficacy

Question 8

What are the two main factors that control drug binding? And what is a dynamic equilibrium in relation to the drug?

Answer 8

1. Speed of the drug reaching the receptor is diffusion controlled
2. Electrostatic, hydrophobic, and hydrogen bonds allow drug to fit to the binding site
3. dynamic equilibrium: how well the receptor binds and how easily it can come off the ligand
   The drug cannot remain bound forever

Question 9

What factors do you have to take into account when dealing with electrostatic and hydrophobic forces?

Answer 9

1. Electrostatic- Charges of the receptor and ligands

2. Hydrophobic- Is the drug hydrophilic or lipophilic

Question 10

How do you measure drug binding using ligand binding assays?

Answer 10

1. Use a detectable ligand with a radioactive or fluorescent tag (L)
2. Source of receptors (R) from tissues or membrane cells
3. Measure the binding of ligand and receptor (RL)

R + L RL

Question 11

What graph is normally used to record binding?

Answer 11

Scatchard Plot

Question 12

Describe what Kd means?

Answer 12

1. The equilibrium dissociation constant
2. Concentration of the ligand to bind 50% of available sites
3. Determined by the forward rate of association and the reverse rate of dissociation of the receptor

(Affinity)

The lower the Kd value the higher the affinity

Question 13

What can you use a competitive binding ligand assay for?

Answer 13

1. Use it to compare the use of a drug to see how well it binds to the receptor

Question 14

Describe what Ki represents?

Answer 14

1. The concentrating of the repeating ligand to displace the 50% of the specific binding of the original normal ligand (radio ligand)
2. Gives an estimate of affinity as assay conditions affect it such as the concentration of the radio ligand

Question 15

What are the three factors that make a drug selective or not?

Answer 15

1. Ability activate the receptor –potency and efficacy
2. Where the drug binds to the receptor (may be multiple biding sites)
3. Tissue selectivity (can the drug get to where the receptor is?)

Question 16

What is a method commonly used to measure a drug response and what can you get from test?

Answer 16

1. The organ bath experiment

2. Produce a concentration response curve and the EC50 and IC50 values

Question 17

What is the EC50 value and what does in terms of an agonist?

Answer 17

1. Concentration of a drug to that causes half the maximal effect produced by that drug
2. A measure of potency of an agonist