What is the area that agonists and competitive inhibitors bind to?
allosteric binding site or orthosteric binding site
What is antagonism?
substance binds to a receptor and influences its response to an agonist
What are mechanisms of competitive antagonists
a higher concentration of agonist is required to generate a given response, but efficacy is not changed
- changes the EC50, but not Emax
What are mechanisms of non-competitive antagonists?
reduces agonist efficacy but no effect on potency
- reduces Emax but not EC50
What are competitive antagonists?
- occupies the same binding site as the agonist, but doesn’t elicit a biological response
- at high agonist concentrations, antagonist is displaces and maximal efficacy can be achieved
How can we measure the biological effect of a competitive antagonist
- to generate a Schild plot based on the parameter called the dose ratio or concentration ratio. The dose ratio is the ratio of agonist EC50 in the presence vs absence of antagonist.
- larger concentration of antagonist required a larger concentration of agonist to generate the maximal response.
- the x-intercept is called the pA2 or pKi, and reflects the potency of the antagonist (reflects the shift in the EC50).
How can partial agonist can act as antagonists?
partial agonist also compete with full agonists with binding into receptors, however when concentration of partial agonist is high enough it will replace the full agonists and lead to a decreased response.
What is irreversible competitive antagonism
when an antagonist binds irreversibly to the drug binding site and can’t be displaced which can reduce the efficacy.
What is allosteric potentiation?
some drugs can have a allosteric effect that can potentiate/enhance the effects of an agonist (increased efficacy or potency)
What are allosteric antagonists
- non competitive inhibition is due to antagonist binding at a distinct site from agonist
- binding of antagonist might prevent activation of agonist bound receptor
- might alter the properties of the agonist binding site, leading to a combination of effects on potency and efficacy
How are allosteric potentiation used in alcohol dependence?
- dependence involves re-modeling in neurons, including down regulation of GABAaR
- symptoms can be anxiety, tremors, delirium, seizures
- benzodiazepines can help to alleviate symptoms and reduce the amount of agonist needed to illicit a higher response
