L06 - Receptors and the effects of drugs

Question 1

What are agonists?

Answer 1

Substances that produce an effect by binding to the receptor

Question 2

What are antagonists?

Answer 2

A substance which interferes with or inhibits the the effects/ physiological action of another (block effects by binding to receptor)

Question 3

What is the patch-clamp technique?

Answer 3

A laboratory technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane

Question 4

Give some examples of competitive antagonists

Answer 4

1. Atropine at muscarinic receptors
2. Propranolol at beta-adrenoceptors
3. Sildenafil at phospho-diesterase 5 (PDE5) competing with cGMP

Question 5

What is the action of competitive antagonists?

Answer 5

• Bind reversibly at the same site as the (natural) agonist

- Produce parallel shift to the right of agonist dose/ response curves

Question 6

What is the action of irreversible antagonists?

Answer 6

• Bind irreversibly at the same site as the agonist
• Forms a covalent bond or binds incredibly tight
• Decreases the maximal response to agonists
• May produce an initial shift to the right of the dose/ response curve with no decrease in max
• Evidence for spare receptors

Question 7

Give some example of irreversible antagonists

Answer 7

1. Phenoxybenzamine at alpha-adrenoceptors

2. Second/ third generation proteasome inhibitors (based on bortezomib)

Question 8

What are the different types of antagonism?

Answer 8

1. Competitive antagonists
2. Irreversible antagonists
3. Allosteric antagonists
4. Channel blockers
5. Physiological antagonists

Question 9

What is the action of allosteric antagonists?

Answer 9

• Bind (reversibly) at a distinct site from the agonist and decrease agonist affinity
• Reduce likelihood of agonist binding

Question 10

What is the action of channel blockers?

Answer 10

• Bind inside the channel (‘plug’) and prevent the passage of ions
• Binding of channel blockers tends to be enhanced by receptor action (use dependence)

Question 11

What is the action of ‘physiological antagonists’?

Answer 11

• Antagonise the physiological effect of some agonists, but via different mechanism

Question 12

Give some examples of allosteric antagonists

Answer 12

1. Gallamine at the muscarinic receptors

2. Beta-carbolines at the GABAA reecptor

Question 13

Give some examples of channel blockers

Answer 13

1. Phencyclidine at the NMDA receptor

Question 14

Give some examples of physiological antagonists

Answer 14

1. Endocrine disruptors - some of the inhibit conjugation reactions
2. Epinephrine and other such substances that are physiological antagonists to histamine
   - Several substances that have anti-histaminergic action despite not being ligands for the histamine receptor

Question 15

What is desensitisation?

Answer 15

Prolonged or repeated exposure to an agonist reduces the response to that drug

Question 16

Give some examples of desensitisation

Answer 16

1. Tolerance to heroin
   - Inc adenylyl cyclase activity in the brain
2. Inactivation of nicotinic receptors
   - Receptor driven into an inactivated site