Dopamine ☺️

Question 1

Describe how dopamine is synthesised

-name a clinically useful drug

Answer 1

RATE LIMITING
Tyrosine from diet =(tyrosine hydroxylase)=> DOPA

DOPA =(DOPA decarboxylase)=> dopamine

-levodopa (crosses BBB, converted to D)

Question 2

Describe how dopamine is stored

-name a clinically useful drug and its use

Answer 2

VMAT1, 2 (D 2H exchanger) => vesicle

-reserpine (blocks VMAT storage, D broken down by MAO)

Question 3

Describe how dopamine is released

-name a clinically useful drug and its use

Answer 3

Ca dependent vesicle release at end terminals and en passant varicosities

-amantadine (D agonist, nicotinic antagonist for Parkinsonism)

Question 4

Describe what 3 receptor types respond to dopamine

-name some clincally useful drugs and its uses

Answer 4

All GPCRs

• D1 like receptor (excitatory neurotransmission) => D1, 5 are coupled to Gs
• D2 like receptor (inhibitory neurotransmission) => D2, 3, 4 are coupled to Gi

Full agonist - apomorphine (non selective morphine agonist in advanced PD) bromocriptine (D2 agonist in PD, hyperprolactinemia, acromegaly, pituitary tumours)

Antagonists - haloperidol, chlopromazine (antipsychotic, N+V)

Question 5

Describe the reuptake of dopamine

-name some clinically useful drugs and their uses

Answer 5

D diffuses to DAT (symport with D, Cl, 2Na)
-gradient driven by NaKATPase

Bupropion (NRT)
Methylpenidate/ritalin (ADHD)

Question 6

Describe the degradation of dopamine

-name some clinically useful drugs and their uses

Answer 6

Majority of D =(MAO, aldehyde dehydrogenase)=> dihydroxyphenylacetic acid =(COMT)=> homovanillic acid

Some D =(COMT)=> 3-methoxydopamine =(MAO, aldehyde dehydrogenase)=> homovanillic acid

MAOi - phenelzine (depression), selegiline(PD)

COMT - entacapone, tolcapone (PD)

Question 7

Describe the 2 recreational drugs that affect the dopamine pathway

Answer 7

Cocaine, amphetamine => highly addictive due to activation of dopamine pathway

Question 8

How are these diseases implicated in dopamine signalling

• Parkinsons
• Schizophrenia
• N+V
• Hormonal disturbances

Answer 8

Parkinsons => loss of D secreting neurones leading to motor symptoms

Schizophrenia => psychosis caused by too much dopamine

N+V => D2 activation may cause nausea

Hormonal disturbances => dopamine agonists inhibit PRL, GH secretions

Question 9

Describe the location of release

What structures are innervated

Answer 9

Substancia nigra and ventral tegmental area => prefrontal cortex, midbrain

Question 10

Which areas of the brain are affected in PD

Answer 10

Dopaminergic pathway in substancia nigra, basal ganglia, caudate, putamen