Drug target sites 2 Flashcards
Do powerful agonists need to occupy all the receptors to produce the maximum response?
No
How many receptors do agonists need to occupy to produce a maximum response?
<5% of the total receptor population
What is a receptor reserve?
An excess of receptors i.e. spare receptors
What does the concept of spare receptors explain the existence of?
Full and Partial Agonists
What do full agonists do in terms of receptors?
Full agonists occupy a small percentage of the receptors to produce the maximum response- they have high efficacy
What do partial agonists do in terms of receptors?
Partial agonists cannot produce the maximum response even when they occupy all the receptors- they have low efficacy
What can non-competitive antagonists do?
Act at a different site from the receptor in the pathway leading to the response
Activate an opposing Physiological mechanism
Interact chemically with the agonist
What must receptors possess the capacity to do?
Spontaneously adopt the active site
What is implied by receptors ability to spontaneously adopt an active site?
There is some level of constitutive activity
What are mutations that enhance receptor constitutive activity associated with?
Disease
What is an inverse agonist?
A ligand that binds to the receptor and limits such constitutive activity
What is ‘orthosteric’?
Ligands that bind to the same region of a receptor as the natural hormone or neurotransmitter
What is ‘allosteric’?
Other sites on receptors to which synthetic ligands may bind
What do ‘allosteric’ ligands do?
Do not produce an effect in isolation
But only modulate the effect of an orthosteric ligand
What kinds of allosteric ligands are there?
Positive
Negative
Neutral
What are positive allosteric ligands?
Ligands that enhance the function of an orthosteric ligand
What are negative allosteric ligands?
Ligands that reduce the function of an orthosteric ligand
What are neutral allosteric ligands?
Ligands that bind but do not alter the function of an orthosteric ligand
How do allosteric ligands produce positive or negative effects?
Increasing/decreaseing the potency of an orthosteric ligand (therefore requiring less/more orthosteric ligand to produce an effect)
Increasing/decreasing the efficacy of an orthosteric ligand (therefore increasing/decreasing the maximal effect of an orthosteric ligand)
What is efficacy?
Capacity for beneficial change of a given intervention
What increases heart rate?
Sympathetic nervous system
Adrenalin
What decreases heart rate?
Parasympathetic nervous system releases acetylcholine
Acetylcholine acts as antagonist
What is EC50?
Effect Concentration (50% maximum response) Concentration of agonist required to get half the maximum response, higher EC50, lower potency
