Receptor Lecture 3 – Receptor antagonists and modulators: tuning a response Flashcards
Antagonist
a ligand that binds to but does not activate a receptor
Competitive Antagonists
Compete with agonist for same receptor binding site
Can be reversible or irreversible
Reversible – increasing agonist concentration can outcompete antagonist
In presence of antagonist, a higher concentration of Agonist A is required to evoke same response
Characteristic shift in agonist concentration-response curve
In presence of antagonist, a higher concentration of Agonist A is required to evoke same response
Characteristic shift in agonist concentration-response curve
Irreversible – antagonist permanently binds to receptor, no amount of agonist will dislodge
In presence of antagonist, higher concentration of Agonist A cannot supplant antagonist
Reduced response
Characteristic suppression of agonist concentration-response curve
With increasing concentrations of antagonist:
Emax of agonist A reduces
EC50 of agonist A gets larger
Affinity
how well a drug binds to a receptor
Efficacy
how well a drug activates a receptor
Orthosteric site
Agonists and competitive antagonists bind at the same site on receptor
Allosteric site
Other drugs/molecules can bind to other sites on receptor and modify effects of agonist
Affinity modulation
Affects how the agonist binds to orthosteric site
Affinity allosteric modulators alter how well the agonist binds to the receptor
Therefore more/less of agonist required for same response
Shifts concentration response curse left/right
positive affinity shift toe the left
negative affinity modulation shifts to the right
Efficacy modulation
Affects how the agonist activates the receptor
Efficacy allosteric modulators alter how well the agonist activates the receptor
Full response of agonist raised/suppressed
Shifts concentration response curse up/down
positive efficacy modulation- shifts up
negative down
Allosteric agonism
Allosteric modulators that push the receptor into an active conformation
