DT-Web

DB00899 - Remifentanil


Identification
Name Remifentanil
Accession Number DB00899 (APRD01216)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 376.4467
Groups approved
Monoisotopic Weight 376.199822016
Pharmacology
Indication For use during the induction and maintenance of general anesthesia.
Mechanism of action Remifentanil 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.
Absorption Not Available
Protein binding 70% (bound to plasma proteins)
Biotransformation By hydrolysis of the propanoic acid-methyl ester linkage by nonspecific blood and tissue esterases.
Route of elimination Remifentanil 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.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Tranylcypromine Possible increased risk of serotonin syndrome.
Triprolidine The CNS depressants, Triprolidine and Remifentanil, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food Interactions Not Available

Targets


Mu-type opioid receptor
Name Mu-type opioid receptor
Gene Name OPRM1
Pharmacological action yes
Actions agonist
References
  • 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
  • Scott LJ, Perry CM: Spotlight on remifentanil for general anaesthesia. CNS Drugs. 2005;19(12):1069-74. - Pubmed
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • 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
  • Patel SS, Spencer CM: Remifentanil. Drugs. 1996 Sep;52(3):417-27; discussion 428. - Pubmed
DTHybrid score 0.9578
Delta-type opioid receptor
Name Delta-type opioid receptor
Gene Name OPRD1
Pharmacological action unknown
Actions agonist
References
  • 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. Epub 2008 Sep 24. - Pubmed
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.7831
Kappa-type opioid receptor
Name Kappa-type opioid receptor
Gene Name OPRK1
Pharmacological action unknown
Actions agonist
References
  • 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. Epub 2009 Oct 29. - Pubmed
  • 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. Epub 2008 Mar 5. - Pubmed
DTHybrid score 0.7602

Predictions


Id Partner name Gene Name Score
1716 Tripartite motif-containing protein 13 TRIM13 0.115
4512 Cytochrome P450 3A4 CYP3A4 0.1082
4119 Cytochrome P450 2D6 CYP2D6 0.1049
1262 Corticotropin-lipotropin POMC 0.0832
6107 Cytochrome P450 3A7 CYP3A7 0.0588
1588 Multidrug resistance protein 1 ABCB1 0.0474
4118 Cytochrome P450 3A5 CYP3A5 0.0443
4137 Nociceptin receptor OPRL1 0.0389
4924 Cytochrome P450 2C8 CYP2C8 0.0385
319 Opioid receptor, sigma 1 OPRS1 0.0343
4757 Cytochrome P450 2C9 CYP2C9 0.0338
174 Sigma 1-type opioid receptor SIGMAR1 0.0337
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0291
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.0287
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0278
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0247
6030 Cytochrome P450 2B6 CYP2B6 0.024
824 Sodium-dependent serotonin transporter SLC6A4 0.0188
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0186
5838 Transient receptor potential cation channel subfamily V member 3 TRPV3 0.0176
2162 Transient receptor potential cation channel subfamily M member 8 TRPM8 0.0176
1944 Transient receptor potential cation channel subfamily A member 1 TRPA1 0.0176
6016 Cytochrome P450 2C19 CYP2C19 0.0168
1291 cAMP response element-binding protein CREB1 0.0166
341 5-hydroxytryptamine 3 receptor HTR3A 0.0164
4210 Toll-like receptor 4 TLR4 0.015
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.014
587 Serum albumin ALB 0.0137
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0136
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0127
4200 Cytochrome P450 1A2 CYP1A2 0.0121
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0118
590 5-hydroxytryptamine 2C receptor HTR2C 0.0113
6106 Cytochrome P450 2C18 CYP2C18 0.0107
20 Prostaglandin G/H synthase 1 PTGS1 0.01
465 Calmodulin CALM1 0.0097
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0094
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.009
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0088
6145 Solute carrier family 22 member 1 SLC22A1 0.0084
136 Estrogen receptor ESR1 0.0082
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0079
3811 Cytochrome P450 19A1 CYP19A1 0.0079
6078 Neuronal acetylcholine receptor subunit beta-4 CHRNB4 0.0065
4120 NADPH--cytochrome P450 reductase POR 0.006
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0058
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0055
5718 Cytochrome P450 2A6 CYP2A6 0.0053
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0051
318 Alpha-2A adrenergic receptor ADRA2A 0.0048
502 5-hydroxytryptamine 2A receptor HTR2A 0.0046
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0045
492 Histamine H1 receptor HRH1 0.0045
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0044
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.0044
320 5-hydroxytryptamine 1A receptor HTR1A 0.0043
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0041
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0039
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0039
94 5-hydroxytryptamine 4 receptor HTR4 0.0035
6013 Cytochrome P450 2E1 CYP2E1 0.0035
1618 High affinity nerve growth factor receptor NTRK1 0.0034
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0033
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0033
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0033
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0027
885 5-hydroxytryptamine 1B receptor HTR1B 0.0025
789 Alpha-1D adrenergic receptor ADRA1D 0.0023
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0022
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0021
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0019
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0018
556 Alpha-1A adrenergic receptor ADRA1A 0.0018
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