pharmacology mechanism of action side effects

1. MAO & MAO
Inhibitors
ABHIJITH SP
CVAS POOKODE

2. Contents
• 1.What is MAO?
• 2.Where is MAO found?
• 3.What are its isoforms?
• 4.What are the functions of MAO?
• 5.What are MAO Inhibitors?
• 6.Why MAO Inhibitors are used?
• 7.What are the complications and side effects of MAO Inhibitors?
• 8.Cheese Reaction.
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3. What is MAO?
• Monoamine oxidase (MAO) is an enzyme involved in the degradation process for
various monoamines released by neurons and glia cells, including Dopamine,
serotonin and norepinephrine (NE).
• They are found bound to the outer membrane of mitochondria in most cell types
of the body.
• The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and
was named tyramine oxidase.
• The MAOs belong to the protein family of flavin-containing amine
oxidoreductases.
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4. What is MAO?
• MAOs are important in the breakdown of monoamines ingested in food, and also
serve to inactivate monoamine neurotransmitters present in the synapse at excess
quantity.
• Because of the latter, they are involved in a number of psychiatric and neurological
diseases, some of which can be treated with monoamine oxidase
inhibitors (MAOIs) which block the action of MAOs.
• MAO-A is also found in the liver, pulmonary vascular endothelium, gastrointestinal
tract, and placenta.
• MAO-B is mostly found in blood platelets.
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5. What are its isoforms?
• MAO-A and MAO-B are the two isoforms.
• MAO-A mainly degrades and involved in the metabolism of
Norepinephrine, Epinephrine, Serotonin, Melatonin.
• MAO-B mainly degrades and involved in the metabolism of
Phenethylamine and benzylamine.
• Both forms break down dopamine, tyramine, and tryptamine equally.
• Both MAO are involved in the metabolism of biogenic amines.
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6. What are its functions?
• Monoamine oxidases catalyze the oxidative deamination of monoamines.
• MAO-A is particularly important in the catabolism of monoamines ingested
in food.
• MAO converts:
• 1).Adrenaline or noradrenaline to 3,4-Dihydroxymandelic acid
• 2).Dopamine to dihydroxyphenyl acetic acid.
• 3).3-Methoxytyramine to homovanillic acid.
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7. What are its functions?
• They decrease the concentration of amine neurotransmitters in the synapse by breaking
them to byproducts.
• Unusually high or low levels of MAOs in the body have been associated
with schizophrenia, depression, attention deficit disorder, substance abuse, migraines, and
irregular sexual maturation.
• Whenever MAO is more---less serotonin and dopamine.
• Whenever MAO is less-More serotonin and Dopamine.
• Smoking causes MAO-B depletion, mimicking the action of an MAO-B inhibitor.
• Smokers who smoke for emotional relief may therefore be unintentionally treating
depression and/or anxiety that is better addressed by an MAO-B inhibitor.
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8. What are MAO Inhibitors?
• Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of
one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A)
and monoamine oxidase B (MAO-B).
• They are best known as highly efficacious anti-depressants, as well as effective therapeutic
agents for panic disorder and social phobia .
• They are particularly effective in treatment-resistant depression and atypical depression.
• They are also used in the treatment of Parkinson's disease and several other disorders.
• Inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression
and anxiety.
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9. Functions and Uses of MAO Inhibitors
• MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown
of monoamine neurotransmitters and thereby increasing their availability at synapse.
• 1.Used as Anti-Depressants as they block action of MAO, thus the concentration of
dopamine and serotonin increase at synapse.
• 2.It activates superoxide dismutase and catalase enzyme thus removing free radicals affecting
neuronal protection.
• 3. A transdermal patch form of the MAOI selegiline, called Emsam, was approved for use
in depression.
• 4.Used to treat BPD and OCD
• 5.Used to treat Parkinson’s Syndrome.
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10. Examples of Drugs
• 1.Non-selective MAO inhibitors
Inhibit both MAO-A and MAO-B.
Phenelzine (Nardil)
Isocarboxazid (Marplan)
Tranylcypromine (Parnate, Jatrosome)
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11. Examples of Drugs
2.Selective MAO-A Inhibitor
• Clorgiline (Clorgyline)
• Moclobemide (Manerix)
• Bifemelane (Celeport)
3.Selective MAO-B Inhibitor
• Selegiline (Emsam, Zelapar)
• Resagiline (Azilect)
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12. Side effects of MAO inhibitors
• Dry mouth.
• Nausea, diarrhea or constipation
• Headache.
• Drowsiness.
• Insomnia.
• Dizziness or lightheadedness.
• Skin reaction at the patch site.
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13. Cheese Reaction
• This happens in people taking Non-Selective MAO Inhibitors.
• Whenever they take food rich in Tyramine, i.e., Cheese, fish, yeast, beer, wine
• The MAO in gut and liver are inhibited by the inhibitors.
• So Tyramine molecules are not degraded and they get absorbed as such into
the systemic circulation.
• Then they replace Norepinephrine from Sympathetic nerve endings.
• This leads to Hypertensive crisis and Stroke.
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16. Facts and Tips.
• 1. Because COMT inhibitors and non-selective MAO-B (monoamine
oxidase-B) inhibitors are believed to have similar mechanisms of action, they
should not be taken at the same time.
• 2.MOA Inhibitors are used as used as Anti-Depressants.
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17. THANK YOU