Agonist

Question 1

What is an Agonist?

Answer 1

A drug which binds to a receptor and causes receptor activation

Question 2

Give some examples of agonists?

Answer 2

Ab
Adrenergic
Cholinergic
Hormones
Opiates
Neurotransmitters

Question 3

Testing new drugs:
Ligand-receptor binding Assay.
What is it give details? (6)

Answer 3

Radioactive drug binds to specific and non specific sites
Increasing conc of raioactive drug suturates specific sites
Radioligand binding measurement of whether a drug interacts with a specific receptor

Affinity: how sticky how much we need to give for it to bind, ability of a drug and receptor to form a drug receptor complex
Inversly proportional to equilirbrium constant
Higher K=lower affinity and vice versa

Lower K=higher affinity
K: dissociation
Affinity: association

Question 4

What is a response-conc curve

Answer 4

Sigmoidal curve
Potency and efficacy
Hill coefficient

Question 5

What the difference between a full and partial agonist?

Answer 5

Full: 100% efficacy
Partial: 50%–> efficacy and potency decreases

Question 6

How does Varenicline work

Answer 6

Smoking–>nicotine activates cells in reward centre of brain
Nicotine attaches to brain cell receptors, This causes dopamine to release making you feel good
When you quit, there is no nicotine attaching to the receptor, less dopamine is released which can cause withdrawal symptoms and cravings
If you use this drug to quit smoking, it blocks the nicotine receptors. But varenicline still triggers some dopamine release so you dont feel bad.
Nicotine has 100% efficacy
Varenicline has 20% efficacy

Question 7

What is an inverse agonist?

Answer 7

A drug which binds to a constitutively active receptor and reduces receptor activation
It has negative efficacy

Basal activity= activity at the base line
Do more research about it!
REDUCES THE ACTIVATION
Antagonist blocks the effect of an agonist
Inverse agonist reduces activation?!

Question 8

What is the use of inverse agonists in genetic diseases? why are they important in retinal blindness etc.

Answer 8

Constitutively active mutatnts: genetic mutations causes receptor activated in the absence of a ligand

Need for invers agonist:
increases TSH receptor activity
=excessive production of thyroid hormones (hyper-thyroidism)

Loss of inverse agonist:
In the dark, retinal binds to rhodopsin GPCR in cone cells, which reduces constitutive activation of the receptor

Rhodopsin mutation (G90D)
->loss of retinal binding
->constitutive activation
->de-sensitisation
->congenital night blindness

Enzyme linked receptor
Gain OF FUNCTION MUTATION can cause activation even without an enzyme/ligand or/and dimer formation