L16 - Receptor Antagonists And Modulators: Inducing A Response Flashcards
What is an antagonist?
A ligand that binds to but does not activate a receptor
What are competitive antagonists?
They compete with agonist for same receptor binding site
- can be reversible or irreversible
How are competitive antagonists reversible?
Increase agonist concentration can outcompete antagonist
How are competitive antagonists irreversible?
Antagonist permanently binds to receptor
- no amount of agonist will dislodge
What is the curve like for reversible competitive antagonists?
In presence of antagonist
- higher conc of agonist A is required to evoke same response
- shift in curve
What is the Emax and EC50 ike for reversible competitive antagonists in increasing conc of antagonist?
Emax - stays the same
EC50 - gets larger
What is the curve like for irreversible competitive antagonists?
In presence of antagonist
- higher conc of agonist A cannot supplant antagonist
- reduced response
- suppression of curve
What is the Emax and EC50 ike for irreversible competitive antagonists in increasing conc of antagonist?
Emax - reduces
EC50 - gets larger
How to measure antagonism?
Schild plot and pA2
How to use the Schild plot to measure the antagonism?
Way to determine nature and potency of antagonist
- y axis: log(conc of antagonist)
- x axis: log(dose ratio - 1)
What is the eqn to measure the dose ratio?
Dose ratio = EC50 agonist w antagonist / EC50 agonist w/o antagonist
What is the pA2 value determined from?
Where the line intersects the x axis
- negative log value of conc
What is the pA2 eqn?
pA2 = log(DR-1) - log[antagonist]
What does the pA2 measure?
Measure of antagonist potency
What does a higher number of pA2 show?
More potent antagonist
What is pA2 a useful tool for?
Comparing agonist/antagonist pairs
If two antagonist produce same pA2 value, what does it suggest?
They act through same receptor
What does the shape of the schild plot indicate?
Nature of antagonism
What is the shape of the schild plot for competitive antagonism?
Linear
What is the shape of the schild plot for non-competitive antagonism?
Curve increase
What do agonist and competitive antagonist bind to?
Same site on receptor
- orthosteric site
Where do other drugs/molecules bind on receptors? What does it do?
Modify effects of agonist
- allosteric site
What is affinity modulation?
Affects how the agonist binds to orthosteric site
What is the efficacy modulation?
Affects how the agonist activates the receptor
What is the allosteric agonism?
Allosteric modulators that push the receptor into an active conformation
What does affinity allosteric modulator alter?
How well the agonist binds to the receptor
- more/less agonist required for same response
- shifts curve leftt/right
What does efficacy allosteric modulators alter?
How well the agonist activates the receptor
- full response of agonist raise/suppressed
- shifts curve up/down
