Lec4: Acetylcholine esterase receptors

Question 1

What two properties of AChE inhibitors will determine their overall effect?

Answer 1

1. Its chemical properties

2. Strength of the bond it forms with AChE

Question 2

Give the steps as to how organophosphorous compunds are toxic to the human body.

Answer 2

1. Forms very stable phosphorous bonds with AChE, which resist hydrolytic cleavage for hours.
2. ACh builds up in synaptic cleft
3. Paralysis + Respiratory failure due to asphyxiation

Question 3

Which compounds take the following amount of time to be broken down in the active site of AChE:

1. Microseconds
2. 20 minutes
3. Hours or days

Answer 3

1. ACh
2. Physostigmine
3. DFP

Question 4

Name two types of AChE inhibiting drugs with therapeutic potential, and the diseases each treats. Which one can cross blood-brain barrier?

Answer 4

1. Pyridostigmine Bromides (Regonol + Mestinon) –> Myesthenia Gravis
2. Tetrahydroaminoacridine (Tactrine + Cognex) –> Alzheimer’s (therefore, these drugs can cross the blood-brain barrier)

Question 5

What is the general characteristic of diseases like Myesthenia Gravis and Alzheimer’s, and then describe each specifically? How are such diseases treated?

Answer 5

Cholinergic function disorders. Treat by increasing ACh in synapse, so one molecule can activate more receptors.

1. MG = ACh receptor breakdown at neuromuscular endplate leading to muscle weakness = muscle weakness.
2. Alz = brain cell loss.

Question 6

State the 3 step pathway for the production of Serotonin (5HT) from its precursor.

Answer 6

Tryptophan > 5-HTP > 5-HT

Question 7

How is serotonin removed from the synapse?

Answer 7

Not by an enzyme! But by a 5-HT transporter.

Question 8

What determines the extent and duration of serotonin receptor activation at the post-synaptic membrane?

Answer 8

The rate at which 5-HT is removed by the 5-HT transporter on the pre-synaptic membrane.

Question 9

The 5-HT transporter is:

1. Dependent on what ions?
2. Made up of how many transmembrane domains?

Answer 9

1. Na+/Cl-

2. 12

Question 10

Give the steps for transport of serotonin through the serotonin transporter.

Answer 10

1. Na+ binds (required for serotonin binding)
2. Serotonin binds
3. Cl- binds (required for transport through the receptor)
4. All three molecules translocated through membrane and disassociate
5. K+ binds
6. K+ translocated outside of membrane to end cycle

Question 11

What does SSRI stand for and what do they do? What class of drugs are they?

Answer 11

Selective Seritoninary Reuptake Inhibitors

Increase duration of serotonin activity by inhibiting 5-HT transporter (Antidepressants).