Lecture 3: Response, Potency and Efficacy

Question 1

Agonist

Answer 1

-bind to receptor site
-enhanced cellular activity
-induced fit that activates receptor

Question 2

Antagonist

Answer 2

-binds to and blocks receptor site
-blocks natural chemical from binding to receptor
-induced fit that does NOT activate receptor

Question 3

Potency

Answer 3

-dose of drug required to produce particular effect of given intensity
-comparison based on doses that produce SAME effect (usually ED50)
-may be overrated

Question 4

High potency

Answer 4

entire curve shifted left towards lower x values

Question 5

low potency

Answer 5

entire curve shifted right to higher x values

Question 6

Efficacy

Answer 6

-response resulting from DR interaction
-limited by toxicity
-more important than potency

Question 7

Strong agonist

Answer 7

high affinity and high efficacy

Question 8

Higher efficacy

Answer 8

curve reaches closer to 100%
-higher y value

Question 9

lower efficacy

Answer 9

lower y value

Question 10

Partial Agonist

Answer 10

-produce reduced response even at full occupancy
-cannot produce same maximal effect as full agonist
-may competitively inhibit response to full agonist
-related to drug binding. to inactive form of receptor

Question 11

Partial agonist examples

Answer 11

-aripiprazole, D2
-buprenorphine, mu opiate
-buspirone, 5-HT1A

Question 12

partial agonist structural basis

Answer 12

resembles a shape between agonist and antagonist

Question 13

Partial Agonist theory

Question 14

Level of response

Answer 14

full agonist > partial agonist > inactive compound > inverse agonist

Question 15

Heroin Methadone example

Answer 15

-Buprehorphine (partial agonist) binds all receptors and provides about half effect of heroin as treatment for opiod addiction = nowhere for heroin to bind so no withdrawal
-Naloxone (antagonist) blocks all receptors but with no effect = no euphoria = withdrawal

Question 16

Full agonist structure

Answer 16

-fits neatly
-loop c closes in

Question 17

Partial agonist structure

Answer 17

-a bit bigger, sticks out
-loop c can close but not all the way

Question 18

Antagonist structure

Answer 18

-bigger, sticks out of receptor
-loop c cannot close

Question 19

Inactive to active form

Answer 19

Lecture 4 recording

Question 20

As partial agonist concentration increases

Answer 20

more occupancy of receptors
-undos full agonist binding?? idk

Question 21

as full agonist concentration increases

Answer 21

less occupancy of receptors

Question 22

Increase partial concentration

Answer 22

decrease overall response

Question 23

Assumption: adding enough partial agonist or antagonist

Answer 23

displaces full agonist

Question 25

Inverse agonist

Answer 25

-requires constitutive activity (otherwise it's just an antagonist) -opposite response of agonist -inactivates receptor? -full or partial -response can be altered by agonist, partial agonist, antagonist (shared binding site) -stabilize inactive form of receptor -ex: rimonobant (acomplia)-CB1 receptors

Question 26

Inactive receptor + agonist

Answer 26

conformational change of receptor and interaction with G proteins

Question 27

active conformation of receptor w/o agonist + inverse agonist

Answer 27

inactive receptor no interaction with G proteins

Question 28

Rimonobant (acomplia)

Answer 28

-inverse agonist -binds to cannaboid (CB1)receptors -reduced hunger, increased anxiety -oops she never made it to the market

Question 29

activation of CB1 receptors

Answer 29

-THC bind -decreased anxiety, hunger, relaxation

Question 30

constitutive activity

Answer 30

REQUIRED for inverse agonists -active form of receptor

Question 31

constitutive activity absent

Answer 31

same as antagonist

Question 32

constitutive activity present

Answer 32

-inverse agonist lower than antagonist curve -backward s curve

Question 33

Endogenous agonist present

Answer 33

silent antagonist has backward s curve

Question 34

endogenous agonist. absent

Answer 34

silent antagonist straight line

Question 35

constitiutive absent, endogenous agonist absent

Answer 35

no effect from either -straight horizontal line on top

Question 36

constitutive activity, NO endogenous agonist

Answer 36

-silent antagonist no effect -inverse agonist has effect

Question 37

NO constitutive activity, endogenous agonist present

Answer 37

-both have same effect

Question 38

Constitutive activity and endogenous agonist present

Answer 38

-both have effect -inverse agonist has better effect

Question 39

Receptor Antagonism

Answer 39

-DR interaction that interfres with or prevents the development of drug response by agonist -competitive, noncompetitive, irreversible

Question 40

Competitive Antagonism

Answer 40

-competing for active site -reversible by increasing dose -increase concentration shifts curve right

Question 41

Log dose-response curve of AGONIST in presence of competitive antagonist

Answer 41

-shifts right -reduction in effective potency of agonist -need more agonist

Question 42

Schild plot

Answer 42

-ability to calculate KD of ligand to generate P2 value

Question 43

Binding affinity generally correlates with

Answer 43

the potency of antagonists