COMT is an enzyme that breaks down catecholamines like dopamine and norepinephrine. It is produced in the brain and liver. COMT inhibitors prevent the breakdown of levodopa, increasing its availability to treat Parkinson's disease. Common COMT inhibitors include entacapone, opicapone, and tolcapone. COMT inhibitors reduce "off time" for Parkinson's patients but can cause side effects like nausea, low blood pressure, and liver damage with tolcapone.

1. COMT & COMT
Inhibitors
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2. Contents
• 1.What is COMT?
• 2.Functions of COMT
• 3.Reactions of COMT
• 4.COMT Inhibitors.
• 5.Side Effects
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3. What is COMT?
• Catechol-O-methyltransferase is one of several enzymes that
degrade catecholamines (such as dopamine, epinephrine,
and norepinephrine), catecholestrogens, and various drugs and substances
having a catechol structure.
• In humans, catechol-O-methyltransferase protein is encoded by
the COMT gene.
• COMT was first discovered by the biochemist Julius Axelrod in 1957.
• Produced by nerve cells in the brain and also by liver.
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4. Functions of COMT
• Catechol-O-methyltransferase is involved in the inactivation of
the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine).
• The enzyme introduces a methyl group to the catecholamine, which is donated by S-
adenosyl methionine (SAM).
• Any compound having a catechol structure, like catecholestrogens and catechol-
containing flavonoids, are substrates of COMT.
• Levodopa, a precursor of catecholamines, is an important substrate of COMT.
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5. Reactions of COMT
• 1.)Dopamine→ 3-Methoxytyramine
• 2.)DOPAC→ HVA (homovanillic acid)
• 3.)Norepinephrine → Normetanephrine
• 4.)Epinephrine → Metanephrine
• 5.)Dihydroxyphenylethylene glycol(DOPEG)
→ Methoxyhydroxyphenylglycol (MOPEG)
• 6.)3,4-Dihydroxymandelic acid (DOMA) → Vanillylmandelic acid(VMA)
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9. COMT Inhibitors
• A catechol-O-methyltransferase (COMT) inhibitor is a drug that inhibits the
enzyme catechol-O-methyltransferase.
• This enzyme methylates catecholamines such as dopamine, norepinephrine and epinephrine.
It also methylates levodopa.
• COMT inhibitors are indicated for the treatment of Parkinson's disease in combination
with levodopa and an aromatic L-amino acid decarboxylase
inhibitor (e.g. carbidopa or benserazide).
• The therapeutic benefit of using a COMT inhibitor is based on its ability to prevent the
methylation of levodopa to 3-O-methyldopa, thus increasing the bioavailability of levodopa.
COMT inhibitors significantly decrease off time in people with Parkinson's disease also
taking carbidopa/levodopa.
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10. COMT Inhibitors
• Entacapone (Comtan, Comtess, Stalevo)
• Nebicapone
• Nitecapone
• Opicapone (Ongentys)
• Tolcapone (Tasmar)
• Drugs ending with “pone”
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12. Points.
• Entacapone and opicapone are peripheral inhibitors, unable to cross
the blood-brain barrier.
• Tolcapone is able to cross the blood-brain barrier.
• Entacapone and opicapone have not been associated with hepatotoxicity.
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13. Side effects of COMT Inhibitors
• nausea
• orthostatic hypotension
• vivid dreams
• confusion
• hallucinations
• hepatotoxicity (only tolcapone)
• diarrhoea
• drowsiness
• urine discoloration
• dyskinesia
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14. THANK YOU