pharmacology sympathetic system autonomic nervous system

1. COMT & COMT
Inhibitors
ABHIJITH SP
CVAS POOKODE

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