DT-Web

DB00463 - Metharbital


Identification
Name Metharbital
Accession Number DB00463 (APRD00757)
Type small molecule
Description Metharbital was patented in 1905 by Emil Fischer working for Merck. It was marketed as Gemonil by Abbott Laboratories. It is a barbiturate anticonvulsant, used in the treatment of epilepsy. It has similar properties to phenobarbital.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 198.2191
Groups approved
Monoisotopic Weight 198.100442324
Pharmacology
Indication Metharbital is used for the treatment of epilepsy.
Mechanism of action Metharbital binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Signs of overdose include confusion (severe), decrease in or loss of reflexes, drowsiness (severe), fever, irritability (continuing), low body temperature, poor judgment, shortness of breath or slow or troubled breathing, slow heartbeat, slurred speech, staggering, trouble in sleeping, unusual movements of the eyes, weakness (severe).
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 potentiator
References
  • Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. - Pubmed
  • Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. - Pubmed
  • Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. - Pubmed
  • Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 0.8387
Gamma-aminobutyric-acid receptor subunit alpha-2
Name Gamma-aminobutyric-acid receptor subunit alpha-2
Gene Name GABRA2
Pharmacological action yes
Actions potentiator
References
  • Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. - Pubmed
  • Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. - Pubmed
DTHybrid score 0.7847
Gamma-aminobutyric-acid receptor subunit alpha-3
Name Gamma-aminobutyric-acid receptor subunit alpha-3
Gene Name GABRA3
Pharmacological action yes
Actions potentiator
References
  • Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. - Pubmed
  • Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. - Pubmed
DTHybrid score 0.7727
Gamma-aminobutyric-acid receptor subunit alpha-4
Name Gamma-aminobutyric-acid receptor subunit alpha-4
Gene Name GABRA4
Pharmacological action yes
Actions potentiator
References
  • Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. - Pubmed
DTHybrid score 0.7348
Gamma-aminobutyric-acid receptor subunit alpha-5
Name Gamma-aminobutyric-acid receptor subunit alpha-5
Gene Name GABRA5
Pharmacological action yes
Actions potentiator
References
  • Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. - Pubmed
  • Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. - Pubmed
DTHybrid score 0.7828
Gamma-aminobutyric-acid receptor subunit alpha-6
Name Gamma-aminobutyric-acid receptor subunit alpha-6
Gene Name GABRA6
Pharmacological action yes
Actions potentiator
References
  • Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. - Pubmed
  • Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. - Pubmed
DTHybrid score 0.7351
Neuronal acetylcholine receptor subunit alpha-4
Name Neuronal acetylcholine receptor subunit alpha-4
Gene Name CHRNA4
Pharmacological action unknown
Actions antagonist
References
  • Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. - Pubmed
  • Arias HR, Bhumireddy P: Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors. Curr Protein Pept Sci. 2005 Oct;6(5):451-72. - Pubmed
  • Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. - Pubmed
DTHybrid score 0.6905
Neuronal acetylcholine receptor subunit alpha-7
Name Neuronal acetylcholine receptor subunit alpha-7
Gene Name CHRNA7
Pharmacological action unknown
Actions antagonist
References
  • Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. - Pubmed
  • Arias HR, Bhumireddy P: Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors. Curr Protein Pept Sci. 2005 Oct;6(5):451-72. - Pubmed
  • Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. - Pubmed
DTHybrid score 0.6906
Glutamate receptor 2
Name Glutamate receptor 2
Gene Name GRIA2
Pharmacological action unknown
Actions antagonist
References
  • Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. - Pubmed
  • Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. - Pubmed
DTHybrid score 1.306
Glutamate receptor, ionotropic kainate 2
Name Glutamate receptor, ionotropic kainate 2
Gene Name GRIK2
Pharmacological action unknown
Actions antagonist
References
  • Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. - Pubmed
  • Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. - Pubmed
DTHybrid score 0.8356

Predictions


Id Partner name Gene Name Score
6086 Gamma-aminobutyric acid receptor subunit gamma-2 GABRG2 0.189
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.1817
4098 Gamma-aminobutyric-acid receptor subunit beta-1 GABRB1 0.1814
4099 Gamma-aminobutyric-acid receptor subunit beta-3 GABRB3 0.177
6087 Gamma-aminobutyric acid receptor subunit gamma-1 GABRG1 0.1692
6088 Gamma-aminobutyric acid receptor subunit gamma-3 GABRG3 0.1682
142 Gamma-aminobutyric-acid receptor subunit rho-1 GABRR1 0.1681
6093 Gamma-aminobutyric acid receptor subunit delta GABRD 0.1679
6089 Gamma-aminobutyric acid receptor subunit epsilon GABRE 0.1677
6090 Gamma-aminobutyric acid receptor subunit pi GABRP 0.1677
6092 Gamma-aminobutyric acid receptor subunit rho-2 GABRR2 0.1674
6115 Gamma-aminobutyric acid receptor subunit rho-3 GABRR3 0.1672
4512 Cytochrome P450 3A4 CYP3A4 0.1573
6016 Cytochrome P450 2C19 CYP2C19 0.1302
6091 Gamma-aminobutyric acid receptor subunit theta GABRQ 0.1229
6013 Cytochrome P450 2E1 CYP2E1 0.1091
811 Translocator protein TSPO 0.1033
4757 Cytochrome P450 2C9 CYP2C9 0.1024
6030 Cytochrome P450 2B6 CYP2B6 0.0814
4200 Cytochrome P450 1A2 CYP1A2 0.0745
4924 Cytochrome P450 2C8 CYP2C8 0.0692
6081 Neuronal acetylcholine receptor subunit alpha-6 CHRNA6 0.0565
5718 Cytochrome P450 2A6 CYP2A6 0.0548
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0476
20 Prostaglandin G/H synthase 1 PTGS1 0.0409
1588 Multidrug resistance protein 1 ABCB1 0.0388
6107 Cytochrome P450 3A7 CYP3A7 0.0379
3937 Fatty-acid amide hydrolase FAAH 0.0374
4118 Cytochrome P450 3A5 CYP3A5 0.0357
4119 Cytochrome P450 2D6 CYP2D6 0.0277
6106 Cytochrome P450 2C18 CYP2C18 0.0268
172 Potassium channel subfamily K member 1 KCNK1 0.0239
6082 Neuronal acetylcholine receptor subunit beta-3 CHRNB3 0.0176
6080 Neuronal acetylcholine receptor subunit alpha-5 CHRNA5 0.0175
948 Neuronal acetylcholine receptor subunit beta-2 CHRNB2 0.0175
482 Glycine receptor subunit alpha-1 GLRA1 0.0172
923 Glutamate receptor 3 GRIA3 0.0159
4097 Neuronal acetylcholine receptor subunit alpha-9 CHRNA9 0.0158
468 Cytochrome P450 4A11 CYP4A11 0.0157
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0156
6024 Cytochrome P450 1A1 CYP1A1 0.0153
6078 Neuronal acetylcholine receptor subunit beta-4 CHRNB4 0.0151
240 Gamma-aminobutyric acid type B receptor, subunit 1 GABBR1 0.0151
220 Sodium channel protein type 5 subunit alpha SCN5A 0.015
587 Serum albumin ALB 0.0144
705 Glutamate receptor 1 GRIA1 0.0143
241 Calcium-transporting ATPase type 2C member 1 ATP2C1 0.0138
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0134
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0133
537 ATP synthase delta chain, mitochondrial ATP5D 0.0132
158 Sodium channel protein type 1 subunit alpha SCN1A 0.013
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0124
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0116
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0114
1898 Cytochrome P450 1B1 CYP1B1 0.0112
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.011
776 Bile salt export pump ABCB11 0.0108
276 Sodium- and chloride-dependent GABA transporter 1 SLC6A1 0.0104
862 Multidrug resistance-associated protein 1 ABCC1 0.0099
3426 Glutamine synthetase glnA 0.0099
3987 Glutamine synthetase GLUL 0.0099
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0098
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0093
502 5-hydroxytryptamine 2A receptor HTR2A 0.0092
6144 Solute carrier family 22 member 2 SLC22A2 0.0089
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0088
6031 Cytochrome P450 3A43 CYP3A43 0.0082
831 D(2) dopamine receptor DRD2 0.0081
6102 Arylamine N-acetyltransferase 2 NAT2 0.008
6145 Solute carrier family 22 member 1 SLC22A1 0.0079
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0076
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0072
4209 ATP-sensitive inward rectifier potassium channel 8 KCNJ8 0.0069
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0067
382 Glutamate receptor, ionotropic kainate 1 GRIK1 0.0065
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0065
820 Glycine receptor subunit alpha-2 GLRA2 0.0063
474 Acetylcholinesterase ACHE 0.0058
3923 Cholinesterase BCHE 0.0056
6014 Cytochrome P450 2A13 CYP2A13 0.0051
1680 Solute carrier family 2, facilitated glucose transporter member 1 SLC2A1 0.0049
23 D(1A) dopamine receptor DRD1 0.0046
461 Glycine receptor subunit alpha-3 GLRA3 0.0045
318 Alpha-2A adrenergic receptor ADRA2A 0.0045
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0042
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0042
556 Alpha-1A adrenergic receptor ADRA1A 0.0042
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0037
6020 Aldehyde oxidase AOX1 0.0037
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0034
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0034
833 Organic cation/carnitine transporter 1 SLC22A4 0.0034
6147 Solute carrier family 22 member 3 SLC22A3 0.0034
3941 Amine oxidase [flavin-containing] A MAOA 0.0033
2981 Phospholipase A2, membrane associated PLA2G2A 0.0033
3939 Amine oxidase [flavin-containing] B MAOB 0.0032
629 Alpha-2B adrenergic receptor ADRA2B 0.0031
3811 Cytochrome P450 19A1 CYP19A1 0.003
592 Carbonic anhydrase 4 CA4 0.003
118 Organic cation/carnitine transporter 2 SLC22A5 0.003
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0026
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0025
924 Glutamate receptor, ionotropic kainate 3 GRIK3 0.0024
922 Glutamate receptor 4 GRIA4 0.0023
920 Glutamate receptor, ionotropic kainate 5 GRIK5 0.0022
919 Glutamate receptor, ionotropic kainate 4 GRIK4 0.0022
4027 Glutamate receptor delta-1 subunit GRID1 0.0022
4018 Glutamate receptor delta-2 subunit GRID2 0.0022
4025 Mitochondrial glutamate carrier 1 SLC25A22 0.0022
4024 Mitochondrial glutamate carrier 2 SLC25A18 0.0022
1912 Excitatory amino acid transporter 1 SLC1A3 0.0022
664 Glutamate decarboxylase 2 GAD2 0.0022
3890 Glutamate decarboxylase 2 GAD2 0.0022
4016 Excitatory amino acid transporter 5 SLC1A7 0.0022
4019 Excitatory amino acid transporter 4 SLC1A6 0.0022
1047 Excitatory amino acid transporter 2 SLC1A2 0.0022
4026 Aspartyl aminopeptidase DNPEP 0.0022
4022 Glutamate--ammonia ligase domain-containing protein 1 LGSN 0.0022
4021 Probable glutamyl-tRNA synthetase, mitochondrial EARS2 0.0022
4023 N-acetylglutamate synthase, mitochondrial NAGS 0.0022
925 Metabotropic glutamate receptor 4 GRM4 0.0022
926 Metabotropic glutamate receptor 7 GRM7 0.0022
927 Metabotropic glutamate receptor 8 GRM8 0.0022
915 Delta 1-pyrroline-5-carboxylate synthetase ALDH18A1 0.0022
4020 Glutamyl aminopeptidase ENPEP 0.0022
4017 5-oxoprolinase OPLAH 0.0022
357 Carbonic anhydrase 2 CA2 0.0021
830 Glutamate dehydrogenase 2, mitochondrial GLUD2 0.002
625 Glutamate carboxypeptidase 2 FOLH1 0.002
3984 Probable glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial PET112L 0.0019
5 Glutaminase liver isoform, mitochondrial GLS2 0.0019
917 Glutaminase kidney isoform, mitochondrial GLS 0.0019
355 GMP synthase [glutamine-hydrolyzing] GMPS 0.0019
4353 GMP synthase [glutamine-hydrolyzing] guaA 0.0019
3991 Glutamine-dependent NAD(+) synthetase NADSYN1 0.0019
3982 Phosphoribosylformylglycinamidine synthase PFAS 0.0019
5261 Phosphoribosylformylglycinamidine synthase purL 0.0019
668 Glutamate--cysteine ligase regulatory subunit GCLM 0.0019
251 Alcohol dehydrogenase 1A ADH1A 0.0019
665 Phosphoserine aminotransferase PSAT1 0.0019
4652 Phosphoserine aminotransferase serC 0.0019
3895 Kynurenine--oxoglutarate transaminase 3 CCBL2 0.0019
801 Kynurenine/alpha-aminoadipate aminotransferase mitochondrial AADAT 0.0019
420 Glutamate decarboxylase 1 GAD1 0.0019
3900 Glutamate decarboxylase 1 GAD1 0.0019
465 Calmodulin CALM1 0.0018
448 Vitamin K-dependent gamma-carboxylase GGCX 0.0018
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.0018
916 Metabotropic glutamate receptor 1 GRM1 0.0018
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0018
824 Sodium-dependent serotonin transporter SLC6A4 0.0018
1671 Excitatory amino acid transporter 3 SLC1A1 0.0017
186 Glutamate--cysteine ligase catalytic subunit GCLC 0.0017
83 Alpha-aminoadipic semialdehyde synthase, mitochondrial AASS 0.0017
3877 Growth-inhibiting protein 18 GIG18 0.0017
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0017
210 Bifunctional aminoacyl-tRNA synthetase [Includes: Glutamyl-tRNA synthetase EPRS 0.0017
914 Formimidoyltransferase-cyclodeaminase FTCD 0.0017
426 Aspartate aminotransferase, mitochondrial GOT2 0.0017
763 Tyrosine aminotransferase TAT 0.0016
5493 Tyrosine aminotransferase Not Available 0.0016
444 Alcohol dehydrogenase 1B ADH1B 0.0016
735 Alanine aminotransferase 1 GPT 0.0016
3904 Alanine aminotransferase 2 GPT2 0.0016
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.0016
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0016
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0016
586 Aspartate aminotransferase, cytoplasmic GOT1 0.0016
795 Branched-chain-amino-acid aminotransferase, mitochondrial BCAT2 0.0016
242 Asparagine synthetase [glutamine-hydrolyzing] ASNS 0.0015
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0015
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
574 Branched-chain-amino-acid aminotransferase, cytosolic BCAT1 0.0015
33 Cystine/glutamate transporter SLC7A11 0.0015
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0015
280 4-aminobutyrate aminotransferase, mitochondrial ABAT 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
738 Monocarboxylate transporter 1 SLC16A1 0.0012
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0012
6151 Monocarboxylate transporter 10 SLC16A10 0.0011
2207 Rhodopsin RHO 0.001
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