Applied neuropharmacology

Question 1

Describe what happens between the pre-synaptic terminal and the post-synaptic terminal in terms of neurotransmitters

Answer 1

• Neurotransmitter is synthesised and packaged in the pre-synaptic cell
• Action potential reaches the pre-synaptic cell
• This causes the calcium voltage gated channels to open
• Increase in conc of calcium in the pre-synaptic cell
• Neurotransmitter moves towards and fuses with the pre-synaptic membrane
• Neurotransmitter released via exocytosis
• NT moves across the synaptic cleft and binds to the post-synaptic membrane (binds to ionotrophic/ metabotorphic receptors)
• NT is inactivated either by uptake in neurones/glia or extracellular breakdown

Question 2

How can the NT process be manipulated to increase NT action through drugs

Answer 2

• Increase packaging/ release of neurotransmitter
• Increase action of post-synaptic receptors with agonist
• Increase effect of the NT on the post-synaptic receptor- e.g. opening time of channel
• Block breakdown of NT
• Block the uptake of NT into pre-synaptic cell

Question 3

How can the NT process be manipulated to decrease the NT action through drugs

Answer 3

• Block Na+ channels
• Block Ca 2+ channels
• Activate pre-synaptic inhibitory receptors
• Block packing
• Block release system
• Block post-synaptic receptors
• Increase breakdown of NT
• Increase uptake back into pre-synaptic cell

Question 4

Which are the main NTs

Answer 4

• Ach
• Monoamine
• Aminoacids
• Purines
• NO
• Neuropeptides

Question 5

Examples of monoamines

Answer 5

Noradrenaline (re-uptake are antidepressant)
Dopamine
Serotonin (re-uptake are antidepressant)

Question 6

Examples of AA

Answer 6

Glycine
Glutamate
GABA

Question 7

Examples of purines

Answer 7

ATP

Adenosine

Question 8

Examples of neuropeptides

Answer 8

Endorphines

CCK

Question 9

Why do different NTs have different actions

Answer 9

Have different anatomical distributions

Bind to different receptors

Question 10

Anatomical distribution of dopamine

Answer 10

• Basal ganglia
• Brainstem
• Limbic system and frontal cortex

Question 11

Physiological functions of dopamine

Answer 11

• Voluntary movement
• Vomiting
• Emotions

Question 12

Which are the key stages in the production of dopamine?

Answer 12

Tyrosine to Dihyroxyphenanine (DOPA)

DOPA to dopamine

Question 13

Which stage is blocked in the production of dopamine?

Answer 13

In parkinsons tyrosine to DOPA step is blocked through degeneration

Question 14

What is dopamine broken down by and into?

Answer 14

• Broken down into homovanillic acid

- Two main enzymes involved: MAO B and COMT

Question 15

Drugs used to improve conditions of Parkinson’s

Answer 15

Precursor: LEVODOPA 
Agonists:
Ergots 
Non-ergots 
Apomorphine
Enzyme inhibitors: 
MAO-B Inhibitors
COMT Inhibitors
Peripheral AAD inhibitors

Question 16

What actions do dopanimergic drugs have?

Answer 16

Improve
Motor features of Parkinson’s: limb rigidity, bradykinesia, tremor

Worsen:
Nausea
Psychosis
Impulsivity

Do not affect:
Midline features: dysarthria, balance, cognition

Question 17

What actions do dopamine antagonists have

Answer 17

Improve:
Vomiting
Nausea
Psychosis

Worsen:
Parkinsonism

Question 18

Compromise dopamine antagonist

Answer 18

DOPERIDONE
Does not cross the blood brain barrier 
Can reach the area postrema which control nausea
Is an anti-emetic= prevents vomiting
Is a DA antagonist

Question 19

What do peripheral AAD inhibitors do??

Answer 19

They inhibit the side effects of levodopa, Increasing the release of levodopa to the CNS

Question 20

Examples of ERGOTS

Answer 20

Cabergoline
Pergolide
Bromocriptine

Question 21

Examples of Non-ergots

Answer 21

Ropinerole= rope in roll

Question 22

Examples of AAD inhibitors

Answer 22

Carbidopa

Benseride

Question 23

Example of MAO-B inhibitor

Answer 23

Safinamide= saf in mind
Selegalline
Rasagalline