Week 2- Part 4- Mechanisms of drug action (before NT release).

Question 1

How can drugs affect neurotransmission?

Give an example.

Answer 1

By influencing one of the various processes involved in neurotransmitter function.

E.g. by enhancing or inhibiting a particular process- or by blocking processes.

Question 2

What are agonists?

What are antagonists?

Answer 2

Drugs that facilitate the activity of a particular neurotransmitter- enhance.

Drugs that inhibit the activity of a particular neurotransmitter- inhibit or block its effects.

Question 3

Look at the useful diagram in the doc!

Answer 3

Done it?

Question 4

Effect on neurotransmission production:

What is the first?

What has to happen to NTs?

Answer 4

Drug can serve as a precursor.

Have to be synthesised- by enzymes- convert precursor molecules into the transmitter substance.

Dopamine- initially synthesised by tyrosine.

Question 5

Continuation with the first:

What was dopamine initially synthesised by?

Along the way, what is another precursor of dopamine?

What can be increased by administering a precursor?

Answer 5

Tyrosine.

Levodopa (L-DOPA).

Rate of synthesis + release of a neurotransmitter- e.g. give someone a lot of L-DOPA, means more dopamine will get synthesised.

Question 6

Continuation with the first:

What is L-DOPA used to treat?

Answer 6

Parkinson’s disease- some symptoms of parkinson’s is due to reduced levels of dopaminergic activity- can be alleviated by the administration of L-DOPA.

Question 7

Continuation with the first:

What is a precursor for serotonin?

What is there evidence for?

By administering a serotonin precursor, what can you do?

Look at the doc for a list of precursors.

Answer 7

Tryptophan is the precursor- can get it from your diet.

Evidence that serotonin precursors- L- tryptophan and 5- hydroxytryptophan- have efficacy in treating depression.

Increase the amount of serotonin that is being synthesised.

Question 8

What is the second?

Give an example.

What can drugs do?

Answer 8

NTs synthesised from precursors by enzymes- drugs can inactivate enzymes and prevent synthesis.

PCPA- a selective and irreversible inhibitor of tryptophan hydroxylase- this prevents the hydroxylation of tryptophan, an important step in the synthesis of serotonin (cant produce it).

Block the effects of an enzyme in the production of a neurotransmitter.

Question 9

Continuation from the second:

What does PCPA cause?

Can PCPA be used medically and not psychologically?

Answer 9

Serotonin depletion- has unpleasant side effects on people’s mood.

Yes.

Question 10

What is the third?

What can some drugs do?

Give an example.

What does the previous do?

What happens as a result?

Answer 10

Drugs can prevent the storage of a transmitter substance in vesicles.

Block and disrupt the storage of neurotransmitters in synaptic vesicles.

Reserpine- Used to lower blood pressure.

Blocks the transporter that moves monoamines into synaptic vesicles for storage.

Monoamine stores are depleted- less gets released.

Question 11

Continuation from the third:

What was it meant to have?

What was this observation important for?

Answer 11

A desired effect of lowering blood pressure- it was claimed that reserpine had an effect on people’s mood, it lowered it.

The development of the monoamine theory of depression- idea that depression is due to reduced levels monoamine.

Question 12

What is the fourth?

What triggers the release of acetylcholine (ACh)?

What does it create?

What does this then trigger?

Answer 12

Some drugs can stimulate the release of NTs.

Substance- latrotoxin- produced by the black widow spider.

Pores in the presynaptic cell membrane that allow CA2+ ions to flow in.

Vesicle fusion and ACh release.

Question 13

Continuation from the fourth:

What is ACh?

What can the venom of a black widow spider do?

Answer 13

A very common neurotransmitter at neuromuscular junctions- when it is released, it can cause muscles to contract.

Can cause you to have involuntary muscle contraction.

Question 14

Fenfluramine:

What does this do?

What was it used as?

What happened to it?

Answer 14

Stimulates the release of serotonin (5-HT) from vesicular storage.

Appetite suppressant (with phentermine in “Fen-Phen”).

Withdrawn from market- in 1997- after association with heart valve disease was identified.

Question 15

MDMA (Methylenedioxymethamphetamine):

What does this do?

What is its popular name?

Answer 15

Stimulates serotonin release.

Ecstasy.

Question 16

What is the fifth?

Give an example.

Answer 16

Drugs can inhibit the release of transmitter substance at the synapse by disrupting how the vesicles fuse with the presynaptic optic cell membrane.

Botulinum toxin- causes botulism- can get it from ingesting contaminated food products.

Question 17

Continuation from the fifth- Botulinum toxin:

What would acetylcholine be considered?

Why?

Where is this particularly important?

What can this be an issue for?

Answer 17

An antagonist.

Prevents the release of acetylcholine at terminal buttons (nerve terminal).

In neuromuscular junctions- it can paralyse muscles, prevents them from working because it prevents acetylcholine release which normally stimulates the muscle to start contracting.

Muscles involved in respiration, it can interfere with breathing.

Question 18

Continuation from the fifth- Botulinum toxin:

What is botulinum toxin produced by?

What does this bacteria produce?

Is it easy to destroy?

Where is it found?

Answer 18

Clostridium botulinum bacteria.

Heat resistant spores that can be found in soil.

Difficult to destroy unless things are prepared properly.

Found in food that has not been processed correctly.

Question 19

Continuation from the fifth- Botulinum toxin:

How does it work?

What does botulinum do?

What does it do the opposite to?

Why?

Answer 19

Vesicles contain ACh- Synaptic vesicles snag onto membrane through snare proteins- fuse membrane- release it into the synaptic cleft- acetylcholine goes across muscle cells- stimulates them to contract.

Break snare proteins- this prevents vesicle fusions- it prevents synaptic vesicles from containing acetylcholine fusing with membrane and releasing contents into the synapse- prevents exocytosis

Black widow spider venom.

Leads paralysis of muscles, including the muscles of breathing.

Question 20

Botulinum toxin poison:

What has botulinum toxin poison been associated with?

How can it be destroyed?

What is harder to kill?

Can it also be in other things, not always in tin goods?

Answer 20

Tinned goods.

With heat.

The spores which produce the toxin.

Yes.

Question 21

Continuation botulinum toxin poison:

What does the disease include?

What is a lethal dose (can kill someone)?

How much can kill the entire population through the oral route?

Where is one surprising thing it is used by people in?

What does it do here?

Answer 21

Food-borne (classical) botulism and wound botulism.

30ng (oral route) or 0.80 to 0.90ug via inhalation.

230g.

Botox (BOtulinum TOXin)- active ingredient here.

Paralyses muscles causing the skin to crunch up and creating wrinkles- the dose is incredibly small however, wont kill you.

Question 22

Continuation botulinum toxin poison:

What else does it treat?

Answer 22

Other processes- under the control of motor neurons (are not just neurons which control muscle contraction)- like sweating + migraine.

Question 23

Frey’s syndrome:

Where can damage be?

How?

What can happen?

Answer 23

Nerve supplying salivary gland.

From surgery to salivary gland- sometimes damage the nerves that control the gland.

It can regrow but to the wrong place- cause sweat on the side of your face when you have food in your mouth.

Question 24

Continuation from frey’s syndrome:

What can kind of nerves are they?

How can this be treated?

What can you say?

Answer 24

Nerves designed to stimulate the production of saliva for example when you have something sour in your mouth like a slice of lemon.

Little injections of botox to paralyse those nerves.

Abnormal axonal regeneration.