Details of the Drug

General Information of Drug (ID: DMZTXCH)

• Drug Name: Remifentanil
• Synonyms: Remifentanyl; Ultiva; GI 87084B; GI 87084X; GI87084B; Remifentanil (INN); Remifentanil [INN:BAN]; Ultiva (TN); Methyl 1-(3-methoxy-3-oxopropyl)-4-(N-propanoylanilino)piperidine-4-carboxylate; 1-Piperidinepropanoic acid, 4-(methoxy-carbonyl)-4-((1-oxopropyl)phenylamino)-, methyl ester; 3-(4-methoxycarbonyl-4-((1-oxopropyl)phenylamino)-1-piperidine)propanoic acid methyl ester; 4-carboxy-4-(n-phenylpropionamido)-1-piperidinepropionic acid dimethyl ester

Indication

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[1], [2]

• Therapeutic Class: Hypnotics and Sedatives
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 376.4
  Topological Polar Surface Area (xlogp); 1.9
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 37 mL/min/kg [4]
  Elimination: 0.1% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1 - 20 minutes [4]
  Metabolism: The drug is metabolized via the nonspecific blood and tissue esterases [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.3% [4]
  Vd: The volume of distribution (Vd) of drug is 0.35 L/kg [6]
• Chemical Identifiers:
  Formula: C20H28N2O5
  IUPAC Name: methyl 1-(3-methoxy-3-oxopropyl)-4-(N-propanoylanilino)piperidine-4-carboxylate
  Canonical SMILES: CCC(=O)N(C1=CC=CC=C1)C2(CCN(CC2)CCC(=O)OC)C(=O)OC
  InChI: InChI=1S/C20H28N2O5/c1-4-17(23)22(16-8-6-5-7-9-16)20(19(25)27-3)11-14-21(15-12-20)13-10-18(24)26-2/h5-9H,4,10-15H2,1-3H3
  InChIKey: ZTVQQQVZCWLTDF-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 60815
  ChEBI ID: CHEBI:8802
  CAS Number: 132875-61-7
  DrugBank ID: DB00899
  TTD ID: D0T5OX
  VARIDT ID: DR00457

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Agonist	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Anaesthesia
• ICD Disease Classification: 9A78.6

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Opioid receptor mu (MOP)	DTT	OPRM1	5.94E-01	-0.02	-0.17

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Remifentanil (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Chlormezanone	DMTWUXR	Major	Additive CNS depression effects by the combination of Remifentanil and Chlormezanone.	Anxiety disorder [6B00-6B0Z]	[18]
Desipramine	DMT2FDC	Moderate	Additive serotonergic effects by the combination of Remifentanil and Desipramine.	Attention deficit hyperactivity disorder [6A05]	[19]
Cariprazine	DMJYDVK	Major	Additive CNS depression effects by the combination of Remifentanil and Cariprazine.	Bipolar disorder [6A60]	[18]
Levomilnacipran	DMV26S8	Major	Additive serotonergic effects by the combination of Remifentanil and Levomilnacipran.	Chronic pain [MG30]	[20]
Sertraline	DM0FB1J	Major	Additive serotonergic effects by the combination of Remifentanil and Sertraline.	Depression [6A70-6A7Z]	[20]
Vilazodone	DM4LECQ	Major	Additive serotonergic effects by the combination of Remifentanil and Vilazodone.	Depression [6A70-6A7Z]	[20]
Vortioxetine	DM6F1PU	Major	Additive serotonergic effects by the combination of Remifentanil and Vortioxetine.	Depression [6A70-6A7Z]	[20]
Milnacipran	DMBFE74	Major	Additive serotonergic effects by the combination of Remifentanil and Milnacipran.	Depression [6A70-6A7Z]	[20]
Escitalopram	DMFK9HG	Major	Additive serotonergic effects by the combination of Remifentanil and Escitalopram.	Depression [6A70-6A7Z]	[20]
Desvenlafaxine	DMHD4PE	Major	Additive serotonergic effects by the combination of Remifentanil and Desvenlafaxine.	Depression [6A70-6A7Z]	[20]
OPC-34712	DMHG57U	Major	Additive CNS depression effects by the combination of Remifentanil and OPC-34712.	Depression [6A70-6A7Z]	[18]
Clomipramine	DMINRKW	Moderate	Additive serotonergic effects by the combination of Remifentanil and Clomipramine.	Depression [6A70-6A7Z]	[19]
Doxepin	DMPI98T	Moderate	Additive serotonergic effects by the combination of Remifentanil and Doxepin.	Depression [6A70-6A7Z]	[19]
Maprotiline	DMPWB7T	Moderate	Additive serotonergic effects by the combination of Remifentanil and Maprotiline.	Depression [6A70-6A7Z]	[19]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Remifentanil and Esketamine.	Depression [6A70-6A7Z]	[21]
Mepenzolate	DM8YU2F	Moderate	Additive antimotility effects by the combination of Remifentanil and Mepenzolate.	Digestive system disease [DE2Z]	[22]
Oxybutynine	DMJPBAX	Moderate	Additive CNS depression effects by the combination of Remifentanil and Oxybutynine.	Discovery agent [N.A.]	[23]
Gabapentin	DM6T924	Major	Additive CNS depression effects by the combination of Remifentanil and Gabapentin.	Epilepsy/seizure [8A61-8A6Z]	[24]
Clonazepam	DMTO13J	Major	Additive CNS depression effects by the combination of Remifentanil and Clonazepam.	Epilepsy/seizure [8A61-8A6Z]	[18]
Phenobarbital	DMXZOCG	Major	Additive CNS depression effects by the combination of Remifentanil and Phenobarbital.	Epilepsy/seizure [8A61-8A6Z]	[18]
Dantrolene	DM1D8XY	Major	Additive CNS depression effects by the combination of Remifentanil and Dantrolene.	Fever [MG26]	[18]
Solifenacin	DMG592Q	Moderate	Additive CNS depression effects by the combination of Remifentanil and Solifenacin.	Functional bladder disorder [GC50]	[22]
Tolterodine	DMSHPW8	Moderate	Additive CNS depression effects by the combination of Remifentanil and Tolterodine.	Functional bladder disorder [GC50]	[22]
Belladonna	DM2RBWK	Moderate	Additive antimotility effects by the combination of Remifentanil and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[23]
Suvorexant	DM0E6S3	Major	Additive CNS depression effects by the combination of Remifentanil and Suvorexant.	Insomnia [7A00-7A0Z]	[18]
Amobarbital	DM0GQ8N	Major	Additive CNS depression effects by the combination of Remifentanil and Amobarbital.	Insomnia [7A00-7A0Z]	[18]
Zaleplon	DMGFWSM	Major	Additive CNS depression effects by the combination of Remifentanil and Zaleplon.	Insomnia [7A00-7A0Z]	[18]
Tasimelteon	DMLOQ1V	Major	Additive CNS depression effects by the combination of Remifentanil and Tasimelteon.	Insomnia [7A00-7A0Z]	[18]
Paraldehyde	DMOC1BX	Major	Additive CNS depression effects by the combination of Remifentanil and Paraldehyde.	Insomnia [7A00-7A0Z]	[18]
ITI-007	DMUQ1DO	Major	Additive CNS depression effects by the combination of Remifentanil and ITI-007.	Insomnia [7A00-7A0Z]	[18]
Quazepam	DMY4D87	Major	Additive CNS depression effects by the combination of Remifentanil and Quazepam.	Insomnia [7A00-7A0Z]	[18]
Estazolam	DMZGXUM	Major	Additive CNS depression effects by the combination of Remifentanil and Estazolam.	Insomnia [7A00-7A0Z]	[18]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Remifentanil and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[25]
Remimazolam	DMLVSYX	Major	Additive CNS depression effects by the combination of Remifentanil and Remimazolam.	Labour/delivery anaesthesia complication [JB0C]	[18]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Remifentanil and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[26]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Remifentanil and Flibanserin.	Mood disorder [6A60-6E23]	[27]
Thalidomide	DM70BU5	Moderate	Additive CNS depression effects by the combination of Remifentanil and Thalidomide.	Multiple myeloma [2A83]	[28]
Prasugrel	DM7MT6E	Moderate	Altered absorption of Remifentanil due to GI dynamics variation caused by Prasugrel.	Myocardial infarction [BA41-BA43]	[29]
Metoclopramide	DMFA5MY	Moderate	Additive CNS depression effects by the combination of Remifentanil and Metoclopramide.	Nausea/vomiting [MD90]	[30]
Ondansetron	DMOTQ1I	Major	Additive serotonergic effects by the combination of Remifentanil and Ondansetron.	Nausea/vomiting [MD90]	[31]
Bupropion	DM5PCS7	Major	Increased risk of lowers seizure threshold by the combination of Remifentanil and Bupropion.	Nicotine use disorder [6C4A]	[32]
Sibutramine	DMFJTDI	Major	Additive serotonergic effects by the combination of Remifentanil and Sibutramine.	Obesity [5B80-5B81]	[33]
Lorcaserin	DMG6OYJ	Major	Additive serotonergic effects by the combination of Remifentanil and Lorcaserin.	Obesity [5B80-5B81]	[34]
Dexfenfluramine	DMJ7YDS	Major	Additive serotonergic effects by the combination of Remifentanil and Dexfenfluramine.	Obesity [5B80-5B81]	[20]
Apraclonidine	DMO4PVE	Moderate	Additive CNS depression effects by the combination of Remifentanil and Apraclonidine.	Optic nerve disorder [9C40]	[35]
Flavoxate	DMKV4NL	Moderate	Additive antimotility effects by the combination of Remifentanil and Flavoxate.	Pain [MG30-MG3Z]	[23]
Pimavanserin	DMR7IVC	Major	Additive CNS depression effects by the combination of Remifentanil and Pimavanserin.	Parkinsonism [8A00]	[18]
Orphenadrine	DMW542E	Major	Additive CNS depression effects by the combination of Remifentanil and Orphenadrine.	Parkinsonism [8A00]	[18]
Methylscopolamine	DM5VWOB	Moderate	Additive CNS depression effects by the combination of Remifentanil and Methylscopolamine.	Peptic ulcer [DA61]	[23]
Quetiapine	DM1N62C	Major	Additive CNS depression effects by the combination of Remifentanil and Quetiapine.	Schizophrenia [6A20]	[36]
Mesoridazine	DM2ZGAN	Major	Additive CNS depression effects by the combination of Remifentanil and Mesoridazine.	Schizophrenia [6A20]	[36]
Aripiprazole	DM3NUMH	Major	Additive CNS depression effects by the combination of Remifentanil and Aripiprazole.	Schizophrenia [6A20]	[18]
Iloperidone	DM6AUFY	Major	Additive CNS depression effects by the combination of Remifentanil and Iloperidone.	Schizophrenia [6A20]	[18]
Paliperidone	DM7NPJS	Major	Additive CNS depression effects by the combination of Remifentanil and Paliperidone.	Schizophrenia [6A20]	[18]
Molindone	DMAH70G	Major	Additive CNS depression effects by the combination of Remifentanil and Molindone.	Schizophrenia [6A20]	[18]
Thiothixene	DMDINC4	Major	Additive CNS depression effects by the combination of Remifentanil and Thiothixene.	Schizophrenia [6A20]	[36]
Asenapine	DMSQZE2	Major	Additive CNS depression effects by the combination of Remifentanil and Asenapine.	Schizophrenia [6A20]	[18]
Pimozide	DMW83TP	Major	Additive CNS depression effects by the combination of Remifentanil and Pimozide.	Schizophrenia [6A20]	[18]
Brilinta	DMBR01X	Moderate	Altered absorption of Remifentanil due to GI dynamics variation caused by Brilinta.	Thrombosis [DB61-GB90]	[29]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7292).
• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020630.
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [6] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [7] The pro-nociceptive effects of remifentanil or surgical injury in mice are associated with a decrease in delta-opioid receptor mRNA levels: Prevent... Pain. 2009 Jan;141(1-2):88-96.
• [8] Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci. 2009 Jun 3;29(22):7341-8.
• [9] Antianalgesia: stereoselective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord.J Pharmacol Exp Ther.2005 Sep;314(3):1101-8.
• [10] Clinical pipeline report, company report or official report of signaturerx.
• [11] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [12] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [13] Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain. 2001 Mar;91(1-2):177-87.
• [14] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [15] Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.Biochem Pharmacol.2014 Dec 1;92(3):448-56.
• [16] Drug design and synthesis of a novel kappa opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology. Bioorg Med Chem Lett. 2010 Jan 1;20(1):121-4.
• [17] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 319).
• [18] US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
• [19] Vizcaychipi MP, Walker S, Palazzo M "Serotonin syndrome triggered by tramadol." Br J Anaesth 99 (2007): 919. [PMID: 18006535]
• [20] Achamallah NS "Visual hallucinations after combining fluoxetine and dextromethorphan ." Am J Psychiatry 149 (1992): 1406. [PMID: 1530079]
• [21] Cerner Multum, Inc. "Australian Product Information.".
• [22] Product Information. Levorphanol Tartrate (levorphanol). Sentynl Therapeutics, Solana Beach, CA.
• [23] Product Information. Apadaz (acetaminophen-benzhydrocodone). KemPharm, Inc, Coralville, IA.
• [24] Eckhardt K, Ammon S, Hofmann U, Riebe A, Gugeler N, Mikus G "Gabapentin enhances the analgesic effect of morphine in healthy volunteers." Anesth Analg 91 (2000): 185-91. [PMID: 10866910]
• [25] Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
• [26] Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
• [27] Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
• [28] Product Information. Thalomid (thalidomide). Celgene Corporation, Warren, NJ.
• [29] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [30] Product Information. Reglan (metoclopramide). Wyeth-Ayerst Laboratories, Philadelphia, PA.
• [31] Canadian Pharmacists Association.
• [32] Product Information. Wellbutrin XL (buPROPion). GlaxoSmithKline, Philadelphia, PA.
• [33] Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5. [PMID: 9861909]
• [34] Product Information. Belviq (lorcaserin). Eisai Inc, Teaneck, NJ.
• [35] Product Information. Alphagan (brimonidine ophthalmic). Allergan Inc, Irvine, CA.
• [36] Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.