Anti-depressants: MAO-I

Question 1

Function of Monoamine oxidase inhibitors

Answer 1

Monoamine oxidase (MAO) metabolizes neurotransmitters like noradrenaline (NA) and serotonin (5-HT).

MAOI Effects:

Inhibits MAO, increasing cytoplasmic concentrations of NA and 5-HT.

This increases leakage of amines into the synaptic cleft, boosting neurotransmitter levels.

Question 2

Which drug does MAO-A preferentially bind to?

Which neurotransmitter increases more?

Whats the order of increase between noradrenalin, dopamine and serotonin?

Answer 2

5-HT > NA
higher enzyme affinity for serotonin

so inhibiting MAO-A - substantial increase in 5-HT levels

5-HT > NA > DA

Question 3

What were the early drugs of MAO-I
Why were they problematic?

Answer 3

Early drugs:

Phenelzine
Isocarboxaid

• non specificity
• bind irreversibly

Question 4

Current MAO-A are reversible (RIMA)
What name is this drug?
Why are they better?

Answer 4

Moclobemide

Safer, selective, better tolerated

Allows for degradation of excess NA (reducing adverse effects)

Question 5

What are the side effects of MAO-I

Answer 5

• Postural hypotension (due to peripheral sympathomimetic effects - increased NA in periphery)
• Central stimulation : tremors, excitement, insomnia, convulsions
• Increased appetite, weight gain (5-HT receptor downregulation)
• Antimuscarinic effects: dry mouth, constipation, blurred vision, difficulty urinating

Question 6

What is the tyramine interaction ‘cheese effect’ involved with MAO-I ?

Why did it lead to reversible MAO-I (RIMA) being made

Answer 6

MAO in the GUT is inhibited, tyramine from foods (cheese, wine, meat, yeast) enters the circulation

Tyramine displaces NA from vesicles and causes NA accumulation

Excessive NA can lead to sever hypertension, headaches or intracranial haemorrhage