Comt and comt inhibitors

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 16-09-2020 ABHIJITH SP CVAS POOKODE 2

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. 16-09-2020 ABHIJITH SP CVAS POOKODE 3

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.  16-09-2020 ABHIJITH SP CVAS POOKODE 4

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) 16-09-2020 ABHIJITH SP CVAS POOKODE 5

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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. 16-09-2020 ABHIJITH SP CVAS POOKODE 9

10. COMT Inhibitors Entacapone (Comtan, Comtess, Stalevo) Nebicapone Nitecapone Opicapone (Ongentys) Tolcapone (Tasmar) Drugs ending with “pone” 16-09-2020 ABHIJITH SP CVAS POOKODE 10

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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. 16-09-2020 ABHIJITH SP CVAS POOKODE 12

13. Side effects of COMT Inhibitors nausea orthostatic hypotension vivid dreams confusion hallucinations hepatotoxicity (only tolcapone) diarrhoea drowsiness urine discoloration dyskinesia 16-09-2020 ABHIJITH SP CVAS POOKODE 13

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