Lecture 3

Question 1

What is the area that agonists and competitive inhibitors bind to?

Answer 1

allosteric binding site or orthosteric binding site

Question 2

What is antagonism?

Answer 2

substance binds to a receptor and influences its response to an agonist

Question 3

What are mechanisms of competitive antagonists

Answer 3

a higher concentration of agonist is required to generate a given response, but efficacy is not changed
- changes the EC50, but not Emax

Question 4

What are mechanisms of non-competitive antagonists?

Answer 4

reduces agonist efficacy but no effect on potency
- reduces Emax but not EC50

Question 5

What are competitive antagonists?

Answer 5

• 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

Question 6

How can we measure the biological effect of a competitive antagonist

Answer 6

• 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).

Question 7

How can partial agonist can act as antagonists?

Answer 7

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.

Question 8

What is irreversible competitive antagonism

Answer 8

when an antagonist binds irreversibly to the drug binding site and can’t be displaced which can reduce the efficacy.

Question 9

What is allosteric potentiation?

Answer 9

some drugs can have a allosteric effect that can potentiate/enhance the effects of an agonist (increased efficacy or potency)

Question 10

What are allosteric antagonists

Answer 10

• 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

Question 11

How are allosteric potentiation used in alcohol dependence?

Answer 11

• 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