Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIQ32PKBD)
  Drug Name Entacapone Drug Info Trifluoperazine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiparkinson Agents Antipsychotic Agents
  Structure

 Mechanism of Entacapone-Trifluoperazine Interaction (Severity Level: Moderate)
     Additive CNS depression effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Entacapone Trifluoperazine
      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
  • Additive CNS depression effects by the combination of Entacapone and Trifluoperazine 
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Entacapone Trifluoperazine
      Mechanism 2 Hypotensive effects
Catechol-O-methyl-transferase  Inhibitor 		Hypotensive effects
Calmodulin  Inhibitor
      Key Mechanism Factor 2
Factor Name Catechol-O-methyl-transferase
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Structure Sequence
MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRILNHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCGYSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKYDVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFECTHYQSFLEYREVVDGLEKAIYKGPGSEAGP
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
      Key Mechanism Factor 3
Factor Name Calmodulin-1
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Structure Sequence
MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK
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).
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Entacapone and Trifluoperazine 
     Antagonize the effect of dopaminergic agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Entacapone Trifluoperazine
      Mechanism 3 Dopaminergic agent
Catechol-O-methyl-transferase  Inhibitor 		Antidopaminergic effects
Dopamine receptor  Antagonist
      Key Mechanism Factor 4
Factor Name Catechol-O-methyl-transferase
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Structure Sequence
MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRILNHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCGYSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKYDVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFECTHYQSFLEYREVVDGLEKAIYKGPGSEAGP
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
      Key Mechanism Factor 5
Factor Name Dopamine receptor Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
    Click to Show/Hide
      Mechanism Description
  • Antagonize the effect of Entacapone when combined with Trifluoperazine 

Recommended Action
      Management Concomitant use of dopaminergic drugs with antidopaminergic agents should generally be avoided. If coadministration is necessary, patients should be alerted to the possibility of excessive drowsiness and monitored for potentially diminished therapeutic response to both treatments. Patients treated for Parkinson's disease should generally avoid antidopaminergic agents, particularly phenothiazines and older neuroleptic agents, since these agents may cause extrapyramidal reactions and exacerbate the symptoms of Parkinson's disease. Likewise, patients with a major psychotic disorder should ordinarily not be treated with dopaminergic drugs because of the risk of exacerbating the psychosis with an increase in central dopaminergic tone.

References
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2 Product Information. Dostinex (cabergoline). Pharmacia and Upjohn, Kalamazoo, MI.
3 Product Information. Geodon (ziprasidone). Pfizer US Pharmaceuticals, New York, NY.
4 Product Information. Mirapex (pramipexole). Boehringer Ingelheim, Ridgefield, CT.
5 Product Information. Norprolac (quinagolide). Ferring Inc, North York, IA.
6 Product Information. Parlodel (bromocriptine). Sandoz Pharmaceuticals Corporation, East Hanover, NJ.
7 Product Information. Permax (pergolide). Athena Neurosciences Inc, South San Francisco, CA.
8 Product Information. Reglan (metoclopramide). Wyeth-Ayerst Laboratories, Philadelphia, PA.
9 Product Information. Requip (ropinirole). SmithKline Beecham, Philadelphia, PA.
10 Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc, Rockville, MD.
11 Product Information. Risperdal (risperidone). Janssen Pharmaceutica, Titusville, NJ.
12 Product Information. Seroquel (quetiapine). Zeneca Pharmaceuticals, Wilmington, DE.
13 Product Information. Zyprexa (olanzapine). Lilly, Eli and Company, Indianapolis, IN.
14 Robbins RJ, Kern PA, Thompson TL "Interactions between thioridazine and bromocriptine in a patient with a prolactin-secreting pituitary adenoma." Am J Med 76 (1984): 921-3. [PMID: 6720732]
15 Weingarten JC, Thompson TL "The effect of thioridazine on prolactinoma growth in a schizophrenic man: case report." Gen Hosp Psychiatry 7 (1985): 364-6. [PMID: 4065553]
16 Yahr MD, Duvoisin RC "Drug therapy of parkinsonism." N Engl J Med 287 (1972): 20-4. [PMID: 4555145]