Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIU0CO1NH)
  Drug Name Promethazine Drug Info Opicapone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiallergic Agents Dopaminergic Antiparkinsonism Agents
  Structure

 Mechanism of Promethazine-Opicapone Interaction (Severity Level: Moderate)
     Additive CNS depression effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Promethazine Opicapone
      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 Promethazine and Opicapone 
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Promethazine Opicapone
      Mechanism 2 Hypotensive effects
Alpha-1 adrenergic receptor  Antagonist 		Hypotensive effects
Catechol-O-methyl-transferase  Inhibitor
      Key Mechanism Factor 2
Factor Name Adrenergic receptor alpha-1 Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
    Click to Show/Hide
      Key Mechanism Factor 3
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
      Mechanism Description
  • Additive hypotensive effects by the combination of Promethazine and Opicapone 
     Antagonize the effect of dopaminergic agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Promethazine Opicapone
      Mechanism 3 Antidopaminergic effects
Dopamine receptor  Antagonist 		Dopaminergic agent
Catechol-O-methyl-transferase  Inhibitor
      Key Mechanism Factor 4
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
      Key Mechanism Factor 5
Factor Name Catechol-O-methyl-transferase
×
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
      Mechanism Description
  • Antagonize the effect of Opicapone when combined with Promethazine 

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
1 Mims RB, Scott CL, Modebe O, Bethune JE "Inhibition of L-dopa-induced growth hormone stimulation by pyridoxine and chlorpromazine." J Clin Endocrinol Metab 40 (1975): 256-9. [PMID: 1117978]
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]