MAO Inhibitors

• Tranylcypromine closely resembles dextroamphetamine and retains some of the sympathomimetic effects of amphetamines.

• It has a prolonged duration of action.

• Hydrazides irreversibly bind to the enzyme

MAO.

• They bind Both MAO A and B. Selegeline is selective for MAO B at low doses, but is less selective at higher doses.

Pharmacodynamics

• They block a major intraneuronal degradative pathway for amine neurotransmitters, permitting more amines to accumulate in presynaptic stores and more to be released.

MAO A is primarily responsible for

metabolism of norepinephrine, serotonin and tyramine. MAO B is more selective for dopamine..

• Non-selective inhibition allows tyramine to accumulate Octopamine replaces NE in the storage vesicles and can result in severe hypotension.

PK of MAO inhibitors

• All are readily absorbed from the GIT.

• Phenelzine is acetylated in the liver, which may be slow or fast depending on genetics.

• Inhibition of MAO continues long after the drug can no longer be detected in plasma, taken as 7 days for tranylcypromine, 2-3 weeks for phenelzine and selegeline

Clinical uses

• 1. Especially effective for endogenous depression

• 2. Social phobia

ADRS

• 1. Headache

• 2. Drowsiness

• 3. Dry mouth

• 4. Weight gain

• 5. Postural hypotension

• 6. Sexual disturbances

DI

• 1. Combination with SSRIs may cause serotonin syndrome which may be fatal. The syndrome includes hyperthermia, muscle rigidity, myoclonus and rapid changes in mental and vital signs.

• 2. Tyramine containing foods like wine, cheese, bananas, yeast containing bread should be avoided.