receptor theory 1: ⇒ drug affinity

Question 1

ligand

Answer 1

molecule that binds to a protein → effect

Question 2

agonist

Answer 2

stimulates receptors

Question 3

antagonist

Answer 3

block receptors

Question 4

partial agonist

Answer 4

an agonist which is unable to induce maximal activation of a receptor population, regardless of the amount of drug applied

Question 5

inverse agonist

Answer 5

reduces signalling of that receptor

Question 6

modulators

Answer 6

control increased/decreased open probability

Question 7

false substrate

Answer 7

abnormal compound accumulated

Question 8

efficacy

Answer 8

how well the receptor binds to ligand/drug

Question 9

KD

Answer 9

a constant that defines affinity of a drug for a receptor

⇒ lower if affinity is high

Question 10

occupancy

Answer 10

= no. receptors occupied / total no. receptors (0-1)

Question 11

EC50

Answer 11

concentration of drug at 50% occupancy

Question 12

potency

Answer 12

concentration or amount of the drug required to produce a defined effect

Question 13

pA2

Answer 13

measure of potency of an antagonist

Question 14

affinity

Answer 14

the fraction of a drug bound to receptors at a given concentration

Question 15

dose-ratio

Answer 15

indicates the fold increase of the agonist needed to achieve the same response at a given concentration of antagonist

Question 16

allosteric

Answer 16

the binding of a metabolite at a site other than the chemically active site of a protein

Question 17

Demonstrate understanding of the concept of receptor occupancy

Answer 17

how many of the receptors are occupied by ligands

Question 18

Demonstrate understanding of the concept of drug specificity

Answer 18

how well the drug targets specific receptors and how well it works

Question 19

Demonstrate understanding of the relationship between drug concentration and effect in a biological system

Answer 19

concentration increases effect on systems until receptors are at full occupancy and are saturated

Question 20

Demonstrate understanding of the concept of spare receptors

Answer 20

occupancy is rarely 100% and there are frequently receptors spare

Question 21

Describe different forms of antagonism

Answer 21

• competitive = binds to and blocks agonist site
  
  • irreversible
  • reversible
• non-competitive
  
  • binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor

Question 22

Describe the experimental methods and data analysis methods commonly used to measure drug-receptor interactions radioligand binding assays using radiolabelling

Answer 22

tissue prep + radioligand
incubate
filter
rinse
count
analyse

Question 23

Demonstrate an understanding of the limitations and potential problems encountered when performing drug-binding and concentration-response experiment

Answer 23

• 3H labelling = expensive and difficult
• 125I = short half life, easily degraded, biological activity of ligand can be reduced
• major problem is RATE of dissociation of ligand-receptor complex
• ligand can get stuck to plastic

Question 24

Describe the use of, create and analyse a Scatchard Plot, dose-response curve

Answer 24

TheScatchard analysisplots the total amount of bound ligand divided by its free concentration (B/[L]) against the total bound ligand, B