Receptors As Drug Targets Flashcards
What are receptors?
Receptors are proteins embedded in the cell membrane that bind to chemical messengers and trigger a response inside the cell.
What happens when too many or too few chemical messengers are released?
Too many cause overstimulation; too few lead to sluggish cellular activity.
How do receptors transmit signals?
The natural messenger binds to the receptor, causing an induced fit that triggers a signaling cascade (signal transduction) inside the cell.
Do chemical messengers undergo a chemical reaction with the receptor?
No, they only cause a conformational change in the receptor.
What are receptor agonists?
Drugs that bind to receptors and mimic the action of natural messengers, activating the receptor.
What are receptor antagonists?
Drugs that bind to receptors and prevent the natural messenger from binding, blocking receptor activation.
What are the three key factors in designing an agonist?
1) Correct binding groups, 2) Correct positioning of binding groups, 3) Correct size for the binding site.
What interactions do agonists use to bind receptors?
Van der Waals forces, hydrogen bonds, and ionic bonds.
Why must agonist interactions not be too strong?
If binding is too strong, the neurotransmitter may not leave, preventing receptor reset.
Why is pharmacophore important in agonist design?
It ensures that the binding groups are positioned correctly to maximize receptor interaction.
How does molecule size affect agonist binding?
Molecules that are too large may not fit correctly, while those that are too small may not form enough interactions.
What are allosteric modulators?
Compounds that bind to an allosteric site to enhance or diminish receptor activity without directly activating the receptor.
How do benzodiazepines work as allosteric modulators?
They bind to the allosteric site on the GABAA receptor, enhancing the action of the natural ligand.
How do receptor antagonists work?
They bind to the receptor but prevent activation by either failing to induce a conformational change or distorting the receptor.
How can antagonists act at the binding site?
They can either fit into the binding site without activating the receptor or bind to different regions in the site.
How do allosteric modulators act as antagonists?
They bind outside the active site and decrease receptor activity by modifying receptor conformation.
What is the umbrella effect in receptor antagonism?
The antagonist binds near the active site and physically blocks the natural messenger from binding.
What are partial agonists?
Drugs that bind to receptors and produce a response, but not to the full extent of a full agonist.
Why do partial agonists produce a weaker effect?
They induce a conformational change that is not ideal, leading to reduced receptor activation.
How do partial agonists work at different receptor subtypes?
They can act as an agonist at one receptor subtype and an antagonist at another.
What is an inverse agonist?
A drug that binds to the receptor and induces the opposite effect of a normal agonist.
What is receptor affinity?
A measure of how strongly a drug binds to a receptor, represented by the affinity constant (Ki).
What is receptor efficacy?
The maximum biological effect a drug can produce as a result of receptor binding.
What is receptor potency?
The amount of drug required to achieve a defined biological effect; higher potency means a lower dose is needed.
Does high affinity always mean high efficacy?
No, a drug can bind strongly to a receptor but still produce a weak biological response.
How are affinity, efficacy, and potency measured?
Using dose-response curves, where efficacy is the maximal effect and potency is the dose required to achieve it.
What is EC50?
The concentration of drug required to achieve 50% of its maximum effect.
What is IC50?
The concentration of an inhibitor needed to reduce a biological response or enzyme activity by 50%.
Why is IC50 not always a reliable predictor of EC50?
IC50 measures inhibition, while EC50 measures activation, and they are influenced by different factors.
