ELM5: Agonists to antagonists Flashcards
How does an agonist work?
- Agonist introduced
- Changes in equilibrium and receptor favours an active state
- Binding energy from interaction stabilises active state
What is a functional assay used for ?
To measure what happens when a drug binds
What are the 4 different types of functional assasy?
Cell based biochemical assay
Organ bath assay
Electrophysiology
Whole organism assay
What is a cell based biochemical assay?
Cells grown in lab in plates
Often used for GPCRs
What is an organ bath assay?
Organ removed from animal and put in tissue bath and supplied with nutrients and oxygen
Measure how normal functions change in response to drugs
What is electrophysiology?
Measures how membrane potential of cell changes with drugs
Uses electrodes on or in cell
Measure channel activity
What is a whole organism assay?
Measure changes in behaviour or disease state caused by drugs
See drug in action and factors like absorption and metabolism
What is the concentration-effect?
Using results of assays to plot a group showing relationship between agonist concentration and its effect
What shape is the plot for a concentration effect?
S shaped or sigmoid
What is EC50?
Measure of potency
What is potency?
Concentration or dose of drug needed to produce a specified effect
What is the specified effect in EC50?
50% of Emax for the drug
What is the difference in the measurements used for binding and functional assays?
Binding is KD and Bmax
Functional is EC50 and Emax
What is the difference between potency and affinity?
EC50 is potency and KD is affinity
How can spare receptors change the relationship between Bmax and KD?
Some receptors aren’t activated
Maximum affect isn’t reached
Emax isn’t directly related to Bmax
Emax reached before Bmax
How can spare receptors activating multiple proteins change the relationship between KD and Bmax
One receptor activates multiple proteins
Maximum effect isn’t always maximum binding as can be reached with only a few receptors
Emax reached before Bmax
What do the values of EC50 and Emax depend on ?
Ratio of receptors to G protein
Number of G proteins a receptor activates
How can EC50 be used to compare drug potency?
Small EC50 means high potency
How can we compare selectivity using EC50?
See EC50 value at one receptor compared to another
What is meant by efficacy?
How well a drug activates a receptor once its bound
What are competitive antagonists?
Compete with agonists for receptor binding site
Remain in the site once bound
What is the functional gaddum equation?
Same form used to describe competitive binding but used for antagonists and uses E Emax and EC50
What are the predictions of the functional gaddum equation?
The maximal effect of the agonist is not changed
If antagonist is there you need more agonist to cause an effect
What are reversible competitive agonists?
Eventually leave site
