Receptor Theories

Question 1

What is occupation theory ?

Answer 1

• drugs act on independent binding sites and activate them
• results in a biological response that is proportional to the amount of drug-receptor complex formed

Question 2

When does the biological response cease in occupation theory ?

Answer 2

• when the drug- receptor complex dissociates

Question 3

What is drug effect directly proportional to in occupation theory ?

Answer 3

• Drug effect is directly proportional to number of receptors occupied.

Question 4

Lock and key concept

Answer 4

• key = substrate
• lock = enzyme
• correct fit will react
• in correct substrate means no reaction

Question 5

What is rate theory ?

Answer 5

• the response is proportional to the rate of drug-receptor complex formation

Question 6

What characterises an agonist in rate theory ?

Answer 6

• drug with fast association & fast dissociation

Question 7

What characterises partial agonist in rate theory ?

Answer 7

• drug with intermediate association & intermediate
  dissociation

Question 8

What characterises antagonist in rate theory ?

Answer 8

• drug with fast association & slow dissociation

Question 9

What is induced fit-theory ?

Answer 9

• the receptor’s binding site and the ligand are not always perfectly complementary.
• binding produces a mutual plastic molding of both the ligand and the receptor as a dynamic process
• leads to the receptor’s conformational change, which is then translated into a biological effect, replacing the rigid “lock and key” model.

Question 10

What happens when the drug approaches the receptor in induced fit theory?

Answer 10

• as a drug approaches a receptor, the receptor changes the conformation of its binding site to form a drug-receptor complex

Question 11

What is the macromolecular perturbation theory ?

Answer 11

• 2 types possible :
• a specific conformational perturbation leads to a biological response (agonist)
• a non specific conformational perturbation leads to no biologic response (antagonist).

Question 12

What is the activation-aggregation theory in drug-receptor interactions?

Answer 12

• drug receptor (in the absence of a drug) still exists in an equilibrium between an activated state (Bioactive) and an inactivated state (Bio-inactive)
• agonists bind to the activated state and antagonist
  to the inactivated state

Question 13

What are some molecular-level conceptual models of receptors?

Answer 13

• multi-unit structures (more than 1 protein) = subunits interact in facilitatory + inhibitory ways
• dynamic + mobile receptors = drift in the membrane

Question 14

What is the 2 state receptor model ?

Answer 14

• regardless of presence or absence of ligand, the receptor exists in 2 states
• R (resting state) + R* (activated state)
• 2 states are in equilibrium with each other

Question 15

What normally happens to receptors when no ligand is present ?

Answer 15

• equilibrium lies far to the left (towards R)
• so only a few receptors found in the R* state
• except constituently active receptors

Question 16

What state does an agonist have high affinity for + now does equilibrium shift ?

Answer 16

• has a high affinity for the R* state than for R, and will shift the equilibrium to the right (R*)

Question 17

What state does an antagonist have high affinity for + now does equilibrium shift ?

Answer 17

• has equal affinity for R and R* so does not affect the equilibrium

Question 18

What state does an inverse agonist have high affinity for ?

Answer 18

• Inverse agonists have affinity for R.

Question 19

How does the two-state receptor model differ from the classical occupation theory in relation to agonists ?

Answer 19

• the two-state model, agonists don’t directly activate the receptor but shift the equilibrium toward the R* form (active state)
• whereas in the classical occupation theory, the agonist directly activates the receptor.

Question 20

What is pharmacological activity directly proportional to ?

Answer 20

• pharmacological activity is directly proportional to the rates of dissociation + association not number of receptors occupied