TRANYCLPROMINE - ANTIDEPRESSANT MOLECULE

1. Role of Tranylcypromine in the
treatment of resistant depression

2. HIT once upon a time

5. What is common thing in the list
• Clozapine
• Blonanserin
• Penfluridol
• Nortriptyline
• Pimozide
• Tianeptine
• Opipramol

6. Which was the first antidepressant
discovered ?

7. What is serendipity?

8. Story of MAO-I

9. Classification of MAO-I
MAO-I
MAO-A
Non -
selective
Selective
MAO-B

10. • Nonselective MAO-A/ MAO-B
– Hydrazine (antidepressant)
• Isocarboxazid
• Phenelzine
• Hydracarbazine
– Non-hydrazines
• Tranylcypromine
• Selective MAO-A inhibitors
– Moclobemide
• Selective MAO-B inhibitors
– Selegiline
Classification of MAO-I

11. MAO-A, MAO-B
MAO-A MAO-B
Acts on NE, 5HT
DA, tyramine
Phenylethylamine
and trace amines
DA, tyramine
Mnemonic A for All Beer for DTs
Location Brain Brain
Gut, liver Platelets
Placenta,
skin
Lymphocytes

12. Tyramine metabolism

13. TRANYLCYPROMINE (TCP)
– First clinical trial in 1959
– Introduced as an antidepressant in 1962
– Temporarily withdrawn in 1964 because of the
cheese reaction; later reintroduced
– Available in USA and Europe (Parnate)

14. • Meta-analysis shows that
– TCP>placebo (5 studies)
– TCP=other ADs (18 studies)
– TCP=other ADs in resistant depression (4 studies)
• Also
– TCP effective in atypical depression (many studies)
– TCP effective in bipolar depression with ? low risk
of switch
– May improve negative s/s in schizophenia
TRANYLCYPROMINE (TCP)

15. Comparison with Nortriptyline
Eur Neuropsychopharmacol. 2017 Aug;27(8):714-731.

16. Comparison with other
antidepressants
Eur Neuropsychopharmacol. 2017 Aug;27(8):714-731.

17. ADVERSE EFFECTS
• Commonest AEs are adrenergic AEs
– Dry mouth
– Insomnia
• Also common: dizziness/postural hypotension,
transient palpitations after dosing, sedation
• No increase in appetite, weight
• Few/no sexual AEs
• No dependence potential
• Need to taper and stop

19. MAOIs and Indian food
• Case reports of tyramine reaction with Indian food---
ZERO

20. What about cheddar cheese?
• 100 gm---about 22 mg
tyramine

21. Fermented foods: Idli

22. Fermented foods: Eat with care

23. Cheeses to avoid

24. Pizza

25. • Pizza with plain mozzarella cheese---OK
• Veggie pizza----OK
• Pepperoni (fresh) pizza---OK
• Cottage cheese - OK
Schulman and Walker (1999)

26. Beverages: Good news
• Bottled beer: one or two 330 mL bottles per day
• White wine (preferred): one or two glasses (100 to
120 mL) per day
• Red wine: Better to avoid
May cause benign headache

27. Food
• Fresh chicken, meat, fish, beef---no problem!
Aged, dried, fermented, smoked, pickled
No banana, Avocados, ripe fruits, yogurt

28. Far-Eastern
Tyramine-containing soya-related items:
• Fermented soya bean
• Fermented tofu
• Tofu kept in the fridge for a few days
• Chilli soyabean paste
• Soyabean paste
• Miso
Wing and Chen (1997). PMID: 9169972

29. Use with caution or
avoid in
• Patients with unstable medical comorbidity
• Severe CVS disorders
• High BP
• Liver disease
• Severe renal disease
• Patients who may not adhere to diet/drug
guidelines
• Pregnancy and lactation

30. TCP: PHARMACOKINETICS
• Half-life, 2 h
– So trough levels during treatment are nearly 0.
– So washout in <1 day.
– So monoamine release, monoamine reuptake
mechanisms may be unimportant.
• Steady-state is unnecessary because MAO
inhibition is irreversible.
• Distributed in all organ systems.

31. • Metabolism by ?
TCP: PHARMACOKINETICS

32. Implications of irreversibility
• For duration of action
– For dietary restrictions
– For drug interactions
– For change of treatment
• New enzyme must be synthesized
– First the MAOI must be washed out
– Then, it takes 1-2 weeks for new MAO to be
synthesized and to reach adequate levels

33. TCP: DRUG INTERACTIONS
• Sumatriptan, rizatriptan, almotriptan are
metabolized by MAO-A
– Almotriptan is also metabolized by CYP enzymes
• Use lower doses in patients receiving TCP.
• Avoid concomitant other antidepressants
• Nicotine use
• Benzodiazepines, Valproate

34. DOSING
• Start at 30 mg/day in divided doses.
• If no response, increase by 10 mg/day every 1-
3 weeks.
• Usual dose, 40-60 mg/day
• Maximum dose, 60 mg/day in divided doses.
– Divided dosing reduces AEs such as dizziness,
postural hypotension, etc.