Details of Drug-Drug Interaction
| Drug General Information (ID: DDI0YR9KOX) | |||||||||
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| Drug Name | Trifluoperazine | Drug Info | Safinamide | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antipsychotic Agents | Dopaminergic Antiparkinsonism Agents | |||||||
| Structure | |||||||||
| Mechanism of Trifluoperazine-Safinamide Interaction (Severity Level: Moderate) | |||||||||
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| Additive CNS depression effects Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Trifluoperazine | Safinamide | |||||||
| Mechanism 1 | CNS depression effects | CNS depression effects | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | CNS depression effects | ||||||||
| Factor Description | CNS depressants are drugs that inhibit or suppress brain activity and can reduce mental and physical processes. Excessive CNS depression can lead to decreased heart rate, slow breathing (less than 10 breaths per minute), extreme confusion or loss of memory, nausea and vomiting, poor judgment, blue lips or fingertips, irritability and aggression, and clammy or cold skin. | ||||||||
| Mechanism Description |
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| Additive hypotensive effects Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Trifluoperazine | Safinamide | |||||||
| Mechanism 2 |
Hypotensive effects Calmodulin Inhibitor |
Hypotensive effects Monoamine oxidase-B selective Inhibitor |
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| Key Mechanism Factor 2 | |||||||||
| Factor Name | Calmodulin-1 |
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Structure
Sequence
MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK
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| Gene Name | CALM1 | ||||||||
| Uniprot ID | CALM1_HUMAN | ||||||||
| KEGG Pathway | hsa:801 | ||||||||
| Protein Family | Calmodulin family | ||||||||
| Protein Function |
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335).
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| Key Mechanism Factor 3 | |||||||||
| Factor Name | Monoamine oxidase type B |
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Structure
Sequence
MSNKCDVVVVGGGISGMAAAKLLHDSGLNVVVLEARDRVGGRTYTLRNQKVKYVDLGGSYVGPTQNRILRLAKELGLETYKVNEVERLIHHVKGKSYPFRGPFPPVWNPITYLDHNNFWRTMDDMGREIPSDAPWKAPLAEEWDNMTMKELLDKLCWTESAKQLATLFVNLCVTAETHEVSALWFLWYVKQCGGTTRIISTTNGGQERKFVGGSGQVSERIMDLLGDRVKLERPVIYIDQTRENVLVETLNHEMYEAKYVISAIPPTLGMKIHFNPPLPMMRNQMITRVPLGSVIKCIVYYKEPFWRKKDYCGTMIIDGEEAPVAYTLDDTKPEGNYAAIMGFILAHKARKLARLTKEERLKKLCELYAKVLGSLEALEPVHYEEKNWCEEQYSGGCYTTYFPPGILTQYGRVLRQPVDRIYFAGTETATHWSGYMEGAVEAGERAAREILHAMGKIPEDEIWQSEPESVDVPAQPITTTFLERHLPSVPGLLRLIGLTTIFSATALGFLAHKRGLLVRV
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| Gene Name | MAOB | ||||||||
| Uniprot ID | AOFB_HUMAN | ||||||||
| KEGG Pathway | hsa:4129 | ||||||||
| Protein Family | Flavin monoamine oxidase family | ||||||||
| Protein Function |
Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079). Preferentially degrades benzylamine and phenylethylamine (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079).
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Although often safe and effective, caution is advised during coadministration of MAOIs and phenothiazines, especially during the first few weeks of treatment. Close monitoring for development of hypotension is recommended. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Ambulatory patients should also be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Alcohol should be avoided, since it may increase hypotensive and CNS effects. | ||||||||