Details of Drug-Drug Interaction
| Drug General Information (ID: DDIFQHOEVT) | |||||||||
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| Drug Name | Entacapone | Drug Info | Phenelzine | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antiparkinson Agents | Antidepressants | |||||||
| Structure | |||||||||
| Mechanism of Entacapone-Phenelzine Interaction (Severity Level: Major) | |||||||||
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| Additive hypertensive effects Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Entacapone | Phenelzine | |||||||
| Mechanism 1 |
Hypertensive effects Catechol-O-methyl-transferase Inhibitor |
Hypertensive effects Monoamine oxidase non-selective Inhibitor |
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| Key Mechanism Factor 1 | |||||||||
| Factor Name | Catechol-O-methyl-transferase |
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Structure
Sequence
MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRILNHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCGYSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKYDVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFECTHYQSFLEYREVVDGLEKAIYKGPGSEAGP
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| Gene Name | COMT | ||||||||
| Uniprot ID | COMT_HUMAN | ||||||||
| KEGG Pathway | hsa:1312 | ||||||||
| Protein Family | Class I-like SAM-binding methyltransferase superfamily | ||||||||
| Protein Function |
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Click to Show/Hide
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| Key Mechanism Factor 2 | |||||||||
| Factor Name | Monoamine oxidase | Structure Sequence | |||||||
| Protein Family | Flavin monoamine oxidase family | ||||||||
| Protein Function |
Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity).
Click to Show/Hide
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| Mechanism Description |
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| Additive serotonergic effects Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Entacapone | Phenelzine | |||||||
| Mechanism 2 |
Serotonergic effects Catechol-O-methyl-transferase Inhibitor |
Serotonergic effects Monoamine oxidase non-selective Inhibitor |
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| Key Mechanism Factor 3 | |||||||||
| Factor Name | Catechol-O-methyl-transferase |
×
Structure
Sequence
MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRILNHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCGYSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKYDVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFECTHYQSFLEYREVVDGLEKAIYKGPGSEAGP
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| Gene Name | COMT | ||||||||
| Uniprot ID | COMT_HUMAN | ||||||||
| KEGG Pathway | hsa:1312 | ||||||||
| Protein Family | Class I-like SAM-binding methyltransferase superfamily | ||||||||
| Protein Function |
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Click to Show/Hide
|
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| Key Mechanism Factor 4 | |||||||||
| Factor Name | Monoamine oxidase | Structure Sequence | |||||||
| Protein Family | Flavin monoamine oxidase family | ||||||||
| Protein Function |
Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity).
Click to Show/Hide
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | In general, COMT inhibitors should not be used concurrently with nonselective MAO inhibitors or other agents that possess MAO inhibiting activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAO inhibitor therapy and initiation of treatment with COMT inhibitors. | ||||||||