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Identification
NameRemifentanil
Accession NumberDB00899  (APRD01216)
TypeSmall Molecule
GroupsApproved
Description

Remifentanil (marketed by Abbott as Ultiva) is a potent ultra short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is a specific mu-type-opioid receptor agonist. Hence, it causes a reduction in sympathetic nervous system tone, respiratory depression and analgesia.

Structure
Thumb
Synonyms
REMIFENTANIL
Remifentanyl
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Remifentanil for Injectionpowder for solution2 mgintravenousTeva Canada LimitedNot applicableNot applicableCanada
Remifentanil for Injectionpowder for solution1 mgintravenousTeva Canada LimitedNot applicableNot applicableCanada
Remifentanil for Injectionpowder for solution2 mgintravenousSandoz Canada IncorporatedNot applicableNot applicableCanada
Remifentanil for Injectionpowder for solution1 mgintravenousSandoz Canada IncorporatedNot applicableNot applicableCanada
Remifentanil Hydrochloride for Injectionpowder for solution5 mgintravenousSterimax IncNot applicableNot applicableCanada
Remifentanil Hydrochloride for Injectionpowder for solution2 mgintravenousSterimax Inc2011-09-29Not applicableCanada
Remifentanil Hydrochloride for Injectionpowder for solution1 mgintravenousSterimax Inc2011-09-27Not applicableCanada
Ultivainjection, powder, lyophilized, for solution1 mg/mLintravenousMylan Institutional LLC1996-11-06Not applicableUs
Ultivapowder for solution5 mgintravenousAbbvie Corporation1997-03-172013-10-02Canada
Ultivapowder for solution2 mgintravenousAbbvie Corporation1997-04-072013-10-02Canada
Ultivapowder for solution1 mgintravenousAbbvie Corporation1997-04-072013-10-02Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Remifentanil hydrochloride
ThumbNot applicableDBSALT001450
Categories
UNIIP10582JYYK
CAS number132875-61-7
WeightAverage: 376.4467
Monoisotopic: 376.199822016
Chemical FormulaC20H28N2O5
InChI KeyInChIKey=ZTVQQQVZCWLTDF-UHFFFAOYSA-N
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
IUPAC Name
methyl 1-(3-methoxy-3-oxopropyl)-4-(N-phenylpropanamido)piperidine-4-carboxylate
SMILES
CCC(=O)N(C1=CC=CC=C1)C1(CCN(CCC(=O)OC)CC1)C(=O)OC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids and derivatives
Alternative Parents
Substituents
  • Alpha-amino acid or derivatives
  • Anilide
  • Piperidinecarboxylic acid
  • 4-aminopiperidine
  • Benzenoid
  • Piperidine
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Methyl ester
  • Tertiary carboxylic acid amide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor use during the induction and maintenance of general anesthesia.
PharmacodynamicsRemifentanil is an opioid agonist with rapid onset and peak effect and ultra-short duration of action. The opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone. The analgesic effects of remifentanil are rapid in onset and offset. Its effects and side effects are dose dependent and similar to other opioids. Remifentanil in humans has a rapid blood-brain equilibration half-time of 1 ± 1 minutes (mean ± SD) and a rapid onset of action.
Mechanism of actionRemifentanil is a µ-opioid agonist with rapid onset and peak effect, and short duration of action. The µ-opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone.
Related Articles
AbsorptionNot Available
Volume of distribution
  • 350 mL/kg
  • 452 ± 144 mL/kg [neonates]
  • 223 ± 30.6 mL/kg [adolescents]
Protein binding70% (bound to plasma proteins)
Metabolism

By hydrolysis of the propanoic acid-methyl ester linkage by nonspecific blood and tissue esterases.

Route of eliminationRemifentanil is an esterase-metabolized opioid. The carboxylic acid metabolite is essentially inactive (1/4600 as potent as remifentanil in dogs) and is excreted by the kidneys with an elimination half-life of approximately 90 minutes.
Half life1-20 minutes
Clearance
  • 40 mL/min/kg [young, healthy adults]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Remifentanil Action PathwayDrug actionSMP00416
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6136
Blood Brain Barrier+0.9381
Caco-2 permeable-0.5271
P-glycoprotein substrateSubstrate0.7345
P-glycoprotein inhibitor IInhibitor0.8682
P-glycoprotein inhibitor IINon-inhibitor0.6428
Renal organic cation transporterNon-inhibitor0.7077
CYP450 2C9 substrateNon-substrate0.8041
CYP450 2D6 substrateNon-substrate0.8786
CYP450 3A4 substrateSubstrate0.6963
CYP450 1A2 substrateNon-inhibitor0.9355
CYP450 2C9 inhibitorNon-inhibitor0.8788
CYP450 2D6 inhibitorNon-inhibitor0.8838
CYP450 2C19 inhibitorNon-inhibitor0.8201
CYP450 3A4 inhibitorNon-inhibitor0.7827
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7945
Ames testNon AMES toxic0.7388
CarcinogenicityNon-carcinogens0.8554
BiodegradationNot ready biodegradable0.9428
Rat acute toxicity2.6994 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9589
hERG inhibition (predictor II)Inhibitor0.6126
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Bioniche teoranta
Packagers
Dosage forms
FormRouteStrength
Powder for solutionintravenous1 mg
Powder for solutionintravenous2 mg
Injection, powder, lyophilized, for solutionintravenous1 mg/mL
Powder for solutionintravenous5 mg
Prices
Unit descriptionCostUnit
Ultiva 5 mg vial118.15USD vial
Ultiva 2 mg vial57.2USD vial
Ultiva 1 mg vial30.19USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5019583 No1993-07-122010-07-12Us
US5866591 Yes1998-03-102018-03-10Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.591 mg/mLALOGPS
logP1.75ALOGPS
logP1.52ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)7.51ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area76.15 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity100.56 m3·mol-1ChemAxon
Polarizability40.82 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Jacob Mathew, J. Killgore, “New methods for the synthesis of alfentanil, sufentanil, and remifentanil.” U.S. Patent US20060149071, issued July 06, 2006.

US20060149071
General ReferencesNot Available
External Links
ATC CodesN01AH06
AHFS Codes
  • 28:08.08
PDB EntriesNot Available
FDA labelDownload (380 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcepromazineAcepromazine may increase the hypotensive activities of Remifentanil.
AcetazolamideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Acetazolamide.
AlvimopanThe risk or severity of adverse effects can be increased when Remifentanil is combined with Alvimopan.
AmilorideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Amiloride.
Ammonium chlorideAmmonium chloride may increase the excretion rate of Remifentanil which could result in a higher serum level.
AmphetamineAmphetamine may increase the analgesic activities of Remifentanil.
AzelastineRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Remifentanil.
BendroflumethiazideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Bendroflumethiazide.
BepridilRemifentanil may increase the bradycardic activities of Bepridil.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
BumetanideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Bumetanide.
ButorphanolButorphanol may decrease the analgesic activities of Remifentanil.
CathinoneCathinone may increase the analgesic activities of Remifentanil.
ChlorothiazideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Chlorothiazide.
ChlorthalidoneThe risk or severity of adverse effects can be increased when Remifentanil is combined with Chlorthalidone.
CyclothiazideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Cyclothiazide.
DesmopressinThe risk or severity of adverse effects can be increased when Remifentanil is combined with Desmopressin.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
EluxadolineRemifentanil may increase the activities of Eluxadoline.
Etacrynic acidThe risk or severity of adverse effects can be increased when Remifentanil is combined with Ethacrynic acid.
EthanolRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
EthoxzolamideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Ethoxzolamide.
FurosemideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Furosemide.
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Hydrochlorothiazide.
HydrocodoneRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroflumethiazideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Hydroflumethiazide.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
IndapamideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Indapamide.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Remifentanil.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
MethotrimeprazineRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MetolazoneThe risk or severity of adverse effects can be increased when Remifentanil is combined with Metolazone.
MetyrosineRemifentanil may increase the sedative activities of Metyrosine.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
MirtazapineRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
NadololRemifentanil may increase the bradycardic activities of Nadolol.
NaltrexoneThe therapeutic efficacy of Remifentanil can be decreased when used in combination with Naltrexone.
OrphenadrineRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
ParaldehydeRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineRemifentanil may increase the serotonergic activities of Paroxetine.
PegvisomantThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Remifentanil.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
PhenelzineRemifentanil may increase the serotonergic activities of Phenelzine.
PramipexoleRemifentanil may increase the sedative activities of Pramipexole.
ProcyclidineThe risk or severity of adverse effects can be increased when Procyclidine is combined with Remifentanil.
RamosetronRemifentanil may increase the activities of Ramosetron.
RopiniroleRemifentanil may increase the sedative activities of Ropinirole.
RotigotineRemifentanil may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Remifentanil.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
SpironolactoneThe risk or severity of adverse effects can be increased when Remifentanil is combined with Spironolactone.
SuccinylcholineSuccinylcholine may increase the bradycardic activities of Remifentanil.
SuvorexantRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Remifentanil.
ThalidomideRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
TicrynafenThe risk or severity of adverse effects can be increased when Remifentanil is combined with Ticrynafen.
TorasemideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Torasemide.
TranylcypromineRemifentanil may increase the serotonergic activities of Tranylcypromine.
TriamtereneThe risk or severity of adverse effects can be increased when Remifentanil is combined with Triamterene.
TrichlormethiazideThe risk or severity of adverse effects can be increased when Remifentanil is combined with Trichlormethiazide.
ZolpidemRemifentanil may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Voltage-gated calcium channel activity
Specific Function:
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociati...
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
References
  1. Scott LJ, Perry CM: Remifentanil: a review of its use during the induction and maintenance of general anaesthesia. Drugs. 2005;65(13):1793-823. [PubMed:16114980 ]
  2. Scott LJ, Perry CM: Spotlight on remifentanil for general anaesthesia. CNS Drugs. 2005;19(12):1069-74. [PubMed:16332149 ]
  3. Warner DS, Hindman BJ, Todd MM, Sawin PD, Kirchner J, Roland CL, Jamerson BD: Intracranial pressure and hemodynamic effects of remifentanil versus alfentanil in patients undergoing supratentorial craniotomy. Anesth Analg. 1996 Aug;83(2):348-53. [PubMed:8694317 ]
  4. Guy J, Hindman BJ, Baker KZ, Borel CO, Maktabi M, Ostapkovich N, Kirchner J, Todd MM, Fogarty-Mack P, Yancy V, Sokoll MD, McAllister A, Roland C, Young WL, Warner DS: Comparison of remifentanil and fentanyl in patients undergoing craniotomy for supratentorial space-occupying lesions. Anesthesiology. 1997 Mar;86(3):514-24. [PubMed:9066316 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  6. Hoke JF, Cunningham F, James MK, Muir KT, Hoffman WE: Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs. J Pharmacol Exp Ther. 1997 Apr;281(1):226-32. [PubMed:9103501 ]
  7. Patel SS, Spencer CM: Remifentanil. Drugs. 1996 Sep;52(3):417-27; discussion 428. [PubMed:8875131 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurot...
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
References
  1. Stucke AG, Zuperku EJ, Sanchez A, Tonkovic-Capin M, Tonkovic-Capin V, Mustapic S, Stuth EA: Opioid receptors on bulbospinal respiratory neurons are not activated during neuronal depression by clinically relevant opioid concentrations. J Neurophysiol. 2008 Nov;100(5):2878-88. doi: 10.1152/jn.90620.2008. Epub 2008 Sep 24. [PubMed:18815346 ]
  2. Rodrigues AR, Castro MS, Francischi JN, Perez AC, Duarte ID: Participation of ATP-sensitive K+ channels in the peripheral antinociceptive effect of fentanyl in rats. Braz J Med Biol Res. 2005 Jan;38(1):91-7. Epub 2005 Jan 18. [PubMed:15665994 ]
  3. Poonawala T, Levay-Young BK, Hebbel RP, Gupta K: Opioids heal ischemic wounds in the rat. Wound Repair Regen. 2005 Mar-Apr;13(2):165-74. [PubMed:15828941 ]
  4. Sahin AS, Duman A, Atalik EK, Ogun CO, Sahin TK, Erol A, Ozergin U: The mechanisms of the direct vascular effects of fentanyl on isolated human saphenous veins in vitro. J Cardiothorac Vasc Anesth. 2005 Apr;19(2):197-200. [PubMed:15868528 ]
  5. Darwish M, Tempero K, Kirby M, Thompson J: Pharmacokinetics and dose proportionality of fentanyl effervescent buccal tablets in healthy volunteers. Clin Pharmacokinet. 2005;44(12):1279-86. [PubMed:16372825 ]
  6. Darwish M, Kirby M, Robertson P Jr, Tracewell W, Jiang JG: Pharmacokinetic properties of fentanyl effervescent buccal tablets: a phase I, open-label, crossover study of single-dose 100, 200, 400, and 800 microg in healthy adult volunteers. Clin Ther. 2006 May;28(5):707-14. [PubMed:16861092 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates th...
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
References
  1. Wong GT, Li R, Jiang LL, Irwin MG: Remifentanil post-conditioning attenuates cardiac ischemia-reperfusion injury via kappa or delta opioid receptor activation. Acta Anaesthesiol Scand. 2010 Apr;54(4):510-8. doi: 10.1111/j.1399-6576.2009.02145.x. Epub 2009 Oct 29. [PubMed:19878098 ]
  2. Pascoe JE, Williams KL, Mukhopadhyay P, Rice KC, Woods JH, Ko MC: Effects of mu, kappa, and delta opioid receptor agonists on the function of hypothalamic-pituitary-adrenal axis in monkeys. Psychoneuroendocrinology. 2008 May;33(4):478-86. doi: 10.1016/j.psyneuen.2008.01.006. Epub 2008 Mar 5. [PubMed:18325678 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on May 26, 2016 03:15