L16 - Receptor Antagonists And Modulators: Inducing A Response

Question 1

What is an antagonist?

Answer 1

A ligand that binds to but does not activate a receptor

Question 2

What are competitive antagonists?

Answer 2

They compete with agonist for same receptor binding site
- can be reversible or irreversible

Question 3

How are competitive antagonists reversible?

Answer 3

Increase agonist concentration can outcompete antagonist

Question 4

How are competitive antagonists irreversible?

Answer 4

Antagonist permanently binds to receptor
- no amount of agonist will dislodge

Question 5

What is the curve like for reversible competitive antagonists?

Answer 5

In presence of antagonist
- higher conc of agonist A is required to evoke same response
- shift in curve

Question 6

What is the Emax and EC50 ike for reversible competitive antagonists in increasing conc of antagonist?

Answer 6

Emax - stays the same
EC50 - gets larger

Question 7

What is the curve like for irreversible competitive antagonists?

Answer 7

In presence of antagonist
- higher conc of agonist A cannot supplant antagonist
- reduced response
- suppression of curve

Question 8

What is the Emax and EC50 ike for irreversible competitive antagonists in increasing conc of antagonist?

Answer 8

Emax - reduces
EC50 - gets larger

Question 9

How to measure antagonism?

Answer 9

Schild plot and pA2

Question 10

How to use the Schild plot to measure the antagonism?

Answer 10

Way to determine nature and potency of antagonist
- y axis: log(conc of antagonist)
- x axis: log(dose ratio - 1)

Question 11

What is the eqn to measure the dose ratio?

Answer 11

Dose ratio = EC50 agonist w antagonist / EC50 agonist w/o antagonist

Question 12

What is the pA2 value determined from?

Answer 12

Where the line intersects the x axis
- negative log value of conc

Question 13

What is the pA2 eqn?

Answer 13

pA2 = log(DR-1) - log[antagonist]

Question 14

What does the pA2 measure?

Answer 14

Measure of antagonist potency

Question 15

What does a higher number of pA2 show?

Answer 15

More potent antagonist

Question 16

What is pA2 a useful tool for?

Answer 16

Comparing agonist/antagonist pairs

Question 17

If two antagonist produce same pA2 value, what does it suggest?

Answer 17

They act through same receptor

Question 18

What does the shape of the schild plot indicate?

Answer 18

Nature of antagonism

Question 19

What is the shape of the schild plot for competitive antagonism?

Answer 19

Linear

Question 20

What is the shape of the schild plot for non-competitive antagonism?

Answer 20

Curve increase

Question 21

What do agonist and competitive antagonist bind to?

Answer 21

Same site on receptor
- orthosteric site

Question 22

Where do other drugs/molecules bind on receptors? What does it do?

Answer 22

Modify effects of agonist
- allosteric site

Question 23

What is affinity modulation?

Answer 23

Affects how the agonist binds to orthosteric site

Question 24

What is the efficacy modulation?

Answer 24

Affects how the agonist activates the receptor

Question 25

What is the allosteric agonism?

Answer 25

Allosteric modulators that push the receptor into an active conformation

Question 26

What does affinity allosteric modulator alter?

Answer 26

How well the agonist binds to the receptor - more/less agonist required for same response - shifts curve leftt/right

Question 27

What does efficacy allosteric modulators alter?

Answer 27

How well the agonist activates the receptor - full response of agonist raise/suppressed - shifts curve up/down