DT-Web

DB01205 - Flumazenil


Identification
Name Flumazenil
Accession Number DB01205 (APRD00974)
Type small molecule
Description Fumazenil is an imidazobenzodiazepine derivative and a potent benzodiazepine receptor antagonist that competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex, thereby reversing the effects of benzodiazepine on the central nervous system.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 303.2884
Groups approved
Monoisotopic Weight 303.101919534
Pharmacology
Indication For the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, and where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures. Also for the management of benzodiazepine overdose as an adjunct for appropriate supportive and symptomatic measures.
Mechanism of action Flumazenil, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in man.
Absorption Not Available
Protein binding Protein binding is approximately 50%, mostly (66%) to albumin. Protein binding is reduced in patients with hepatic cirrhosis.
Biotransformation Hepatic. Flumazenil is completely (99%) metabolized. The major metabolites of flumazenil identified in urine are the de-ethylated free acid and its glucuronide conjugate.
Route of elimination Flumazenil is completely (99%) metabolized. Elimination of radiolabeled drug is essentially complete within 72 hours, with 90% to 95% of the radioactivity appearing in urine and 5% to 10% in the feces.
Toxicity In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Gamma-aminobutyric-acid receptor subunit alpha-1
Name Gamma-aminobutyric-acid receptor subunit alpha-1
Gene Name GABRA1
Pharmacological action yes
Actions antagonist
References
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Wingrove PB, Safo P, Wheat L, Thompson SA, Wafford KA, Whiting PJ: Mechanism of alpha-subunit selectivity of benzodiazepine pharmacology at gamma-aminobutyric acid type A receptors. Eur J Pharmacol. 2002 Feb 15;437(1-2):31-9. - Pubmed
  • Whitwam JG, Amrein R: Pharmacology of flumazenil. Acta Anaesthesiol Scand Suppl. 1995;108:3-14. - Pubmed
DTHybrid score 0.3462
Gamma-aminobutyric acid receptor subunit gamma-2
Name Gamma-aminobutyric acid receptor subunit gamma-2
Gene Name GABRG2
Pharmacological action yes
Actions antagonist
References
  • Padgett CL, Lummis SC: The F-loop of the GABA A receptor gamma2 subunit contributes to benzodiazepine modulation. J Biol Chem. 2008 Feb 1;283(5):2702-8. Epub 2007 Oct 31. - Pubmed
  • Wingrove PB, Safo P, Wheat L, Thompson SA, Wafford KA, Whiting PJ: Mechanism of alpha-subunit selectivity of benzodiazepine pharmacology at gamma-aminobutyric acid type A receptors. Eur J Pharmacol. 2002 Feb 15;437(1-2):31-9. - Pubmed
  • Whitwam JG, Amrein R: Pharmacology of flumazenil. Acta Anaesthesiol Scand Suppl. 1995;108:3-14. - Pubmed
DTHybrid score 0.1891
Gamma-aminobutyric-acid receptor subunit alpha-5
Name Gamma-aminobutyric-acid receptor subunit alpha-5
Gene Name GABRA5
Pharmacological action yes
Actions antagonist
References
  • Clement Y, Le Guisquet AM, Venault P, Chapouthier G, Belzung C: Pharmacological alterations of anxious behaviour in mice depending on both strain and the behavioural situation. PLoS One. 2009 Nov 11;4(11):e7745. doi: 10.1371/journal.pone.0007745. - Pubmed
DTHybrid score 0.2463

Predictions


Id Partner name Gene Name Score
423 Gamma-aminobutyric-acid receptor subunit alpha-2 GABRA2 0.2071
580 Gamma-aminobutyric-acid receptor subunit alpha-3 GABRA3 0.2033
530 Gamma-aminobutyric-acid receptor subunit alpha-4 GABRA4 0.1442
841 Gamma-aminobutyric-acid receptor subunit alpha-6 GABRA6 0.1414
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.1288
6087 Gamma-aminobutyric acid receptor subunit gamma-1 GABRG1 0.1284
6088 Gamma-aminobutyric acid receptor subunit gamma-3 GABRG3 0.1256
142 Gamma-aminobutyric-acid receptor subunit rho-1 GABRR1 0.123
6093 Gamma-aminobutyric acid receptor subunit delta GABRD 0.1226
6089 Gamma-aminobutyric acid receptor subunit epsilon GABRE 0.1223
4098 Gamma-aminobutyric-acid receptor subunit beta-1 GABRB1 0.1222
6092 Gamma-aminobutyric acid receptor subunit rho-2 GABRR2 0.1218
6090 Gamma-aminobutyric acid receptor subunit pi GABRP 0.1218
6115 Gamma-aminobutyric acid receptor subunit rho-3 GABRR3 0.1216
4099 Gamma-aminobutyric-acid receptor subunit beta-3 GABRB3 0.1183
4095 Neuronal acetylcholine receptor subunit alpha-7 CHRNA7 0.077
947 Neuronal acetylcholine receptor subunit alpha-4 CHRNA4 0.077
918 Glutamate receptor, ionotropic kainate 2 GRIK2 0.0753
6091 Gamma-aminobutyric acid receptor subunit theta GABRQ 0.074
921 Glutamate receptor 2 GRIA2 0.0684
4512 Cytochrome P450 3A4 CYP3A4 0.0643
811 Translocator protein TSPO 0.0571
4757 Cytochrome P450 2C9 CYP2C9 0.0386
6016 Cytochrome P450 2C19 CYP2C19 0.038
6013 Cytochrome P450 2E1 CYP2E1 0.0376
6030 Cytochrome P450 2B6 CYP2B6 0.0261
482 Glycine receptor subunit alpha-1 GLRA1 0.0249
4924 Cytochrome P450 2C8 CYP2C8 0.0192
6107 Cytochrome P450 3A7 CYP3A7 0.0179
4118 Cytochrome P450 3A5 CYP3A5 0.0168
1588 Multidrug resistance protein 1 ABCB1 0.0165
4119 Cytochrome P450 2D6 CYP2D6 0.0163
4200 Cytochrome P450 1A2 CYP1A2 0.0157
240 Gamma-aminobutyric acid type B receptor, subunit 1 GABBR1 0.0151
241 Calcium-transporting ATPase type 2C member 1 ATP2C1 0.0138
20 Prostaglandin G/H synthase 1 PTGS1 0.0136
537 ATP synthase delta chain, mitochondrial ATP5D 0.0132
6106 Cytochrome P450 2C18 CYP2C18 0.013
587 Serum albumin ALB 0.0129
705 Glutamate receptor 1 GRIA1 0.0127
5718 Cytochrome P450 2A6 CYP2A6 0.0124
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0124
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0116
2981 Phospholipase A2, membrane associated PLA2G2A 0.0108
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0102
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0088
3426 Glutamine synthetase glnA 0.0084
3987 Glutamine synthetase GLUL 0.0084
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0072
4209 ATP-sensitive inward rectifier potassium channel 8 KCNJ8 0.0069
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0065
820 Glycine receptor subunit alpha-2 GLRA2 0.0063
172 Potassium channel subfamily K member 1 KCNK1 0.0061
276 Sodium- and chloride-dependent GABA transporter 1 SLC6A1 0.0057
6102 Arylamine N-acetyltransferase 2 NAT2 0.0056
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0052
1680 Solute carrier family 2, facilitated glucose transporter member 1 SLC2A1 0.0049
3937 Fatty-acid amide hydrolase FAAH 0.0048
6024 Cytochrome P450 1A1 CYP1A1 0.0048
23 D(1A) dopamine receptor DRD1 0.0046
461 Glycine receptor subunit alpha-3 GLRA3 0.0045
382 Glutamate receptor, ionotropic kainate 1 GRIK1 0.0045
318 Alpha-2A adrenergic receptor ADRA2A 0.0045
6031 Cytochrome P450 3A43 CYP3A43 0.0045
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0042
556 Alpha-1A adrenergic receptor ADRA1A 0.0042
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0042
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0039
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0037
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0037
6020 Aldehyde oxidase AOX1 0.0037
468 Cytochrome P450 4A11 CYP4A11 0.0034
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0034
6144 Solute carrier family 22 member 2 SLC22A2 0.0033
629 Alpha-2B adrenergic receptor ADRA2B 0.0031
3811 Cytochrome P450 19A1 CYP19A1 0.003
592 Carbonic anhydrase 4 CA4 0.003
6145 Solute carrier family 22 member 1 SLC22A1 0.0028
502 5-hydroxytryptamine 2A receptor HTR2A 0.0027
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0023
357 Carbonic anhydrase 2 CA2 0.0021
251 Alcohol dehydrogenase 1A ADH1A 0.0019
465 Calmodulin CALM1 0.0018
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0018
824 Sodium-dependent serotonin transporter SLC6A4 0.0018
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0018
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0017
444 Alcohol dehydrogenase 1B ADH1B 0.0016
831 D(2) dopamine receptor DRD2 0.0016
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0016
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0016
1768 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 subunit GNG2 0.0015
1581 G protein-activated inward rectifier potassium channel 2 KCNJ6 0.0015
1268 Neuropeptide S receptor NPSR1 0.0015
1571 G protein-activated inward rectifier potassium channel 1 KCNJ3 0.0015
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0015
1898 Cytochrome P450 1B1 CYP1B1 0.0015
776 Bile salt export pump ABCB11 0.0014
517 Alcohol dehydrogenase 1C ADH1C 0.0014
6073 Potassium channel subfamily K member 9 KCNK9 0.0014
6072 Potassium channel subfamily K member 3 KCNK3 0.0014
862 Multidrug resistance-associated protein 1 ABCC1 0.0013
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0012
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0012
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0011
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.001
2207 Rhodopsin RHO 0.001
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