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Lec 3 - Antagonists & Schild Plot
Terms in this set (16)
what is an antagonist?
a molecule that binds to a receptor and influences the response of the receptor to an agonist
4 main types of antagonists
allosteric antagonist (pure noncompetitive antagonist and mixed antagonist)
irreversible competitive antagonist
binds to the agonist site but does not elicit biological response
decreases potency (EC50)
does not affect efficacy
higher conc. of agonist can be added to offset effects of antagonist and achieve maximal effects
pure noncompetitive antagonist
drug binds to site other than agonist site (allosteric site)
all non-competitive antagonists are allosteric
pure noncomp antagonist - reduces efficacy, not potency
increasing concentration of the drug does not reverse effects of antagonist
binding of the antagonist prevents the activation of the agonist-bound receptor (decreases efficacy)
it results in changing of properties in agonist binding site (e.g. conformational change) - efficacy AND potency
cause a combination of decreased efficacy AND potency
mixed antagonists are allosteric
irreversible competitive antagonist
bind to receptor site (orthosteric site)
reduces efficacy, not potency
how can you measure the effect of an antagonist when it does not produce its own biological effects?
use schild plot - uses 'dose ratio' or 'concentration ratio'
what is a schild plot?
a graph that describes the effects of increasing concentrations of the antagonist on the apparent EC50 (measure potency of antagonist)
EC50 gets larger as the concentration of the antagonist increases
dose ratio = EC50 (antagonist) / EC50 (control)
measures agonist EC50 in the presence vs. absence of antagonist
x intercept shows potency (pA2 or pKi)
how can a partial agonist behave as an antagonist?
when a full agonist and a partial agonist are present, the partial agonist acts as a COMPETITIVE antagonist - potency is decreased
competes with the full agonist for receptor occupancy
because there are only so many receptors, as more and more are occupied by partial agonists, the total response goes down than when observed with the full agonist alone
allosteric binding (site that is distinct from agonist binding/orthosteric site) can have both inhibiting (in the case of non-competitive antagonists) and potentiating outcome (allosteric potentiators)
away from agonist binding site
acts to potentiate/enhance the effects of agonist
increased effiicacy, potency, or both
positive allosteric modulator
(same as allosteric potentiators)
ex - Benzodiazepenes and GABA
GABA receptors suppress activity in nervous system
alcohol abuse = down-regulation of GABA receptors (less GABA receptors)
symptoms of alcohol withdrawal include anxiety, seizures, tremors, etc.
Benzodiazepenes (positive allosteric modulator, separate site) potentiate signals from GABA receptors that are present - alleviates some symptoms
binding vs effect
there is not a direct relationship b/w fraction of receptors bound to a drug, and the response
effect and binding do not necessarily have the same conc. dependence
concentration of a drug needed so that 50% of receptors are bound
why can there be a mismatch between binding and effect?
more receptors present than are required for full effect
difference between binding and effect
happens when there are more receptors present than are required for full effect
extra receptors are there for "backup" in case some receptors fail to function/become occupied by antagonist
THIS SET IS OFTEN IN FOLDERS WITH...
Lec 1 - Introduction
Lec 2 - Agonists, Dose-Response Curve
Lec 4 - Intro to Pharmacokinetics
Lec 5 - How do we know if a drug works?
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