DT-Web

DB00474 - Methohexital


Identification
Name Methohexital
Accession Number DB00474 (APRD00058)
Type small molecule
Description An intravenous anesthetic with a short duration of action that may be used for induction of anesthesia. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 262.3043
Groups approved
Monoisotopic Weight 262.131742452
Pharmacology
Indication Methohexital is indicated for use as an intravenous anaesthetic. It has also been commonly used to induce deep sedation.
Mechanism of action Methohexital 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.
Absorption The absolute bioavailability following rectal administration of methohexital is 17%.
Protein binding 73%
Biotransformation Metabolism occurs in the liver through demethylation and oxidation. Side-chain oxidation is the most important biotransformation involved in termination of biologic activity.
Route of elimination Excretion occurs via the kidneys through glomerular filtration.
Toxicity The onset of toxicity following an overdose of intravenously administered methohexital will be within seconds of the infusion. If methohexital is administered rectally or is ingested, the onset of toxicity may be delayed. The manifestations of an ultrashort-acting barbiturate in overdose include central nervous system depression, respiratory depression, hypotension, loss of peripheral vascular resistance, and muscular hyperactivity ranging from twitching to convulsive-like movements. Other findings may include convulsions and allergic reactions. Following massive exposure to any barbiturate, pulmonary edema, circulatory collapse with loss of peripheral vascular tone, and cardiac arrest may occur.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Aminophylline The barbiturate, methohexital, decreases the effect of aminophylline.
Betamethasone The barbiturate, methohexital, may decrease the effect of the corticosteroid, betamethasone.
Clomifene The enzyme inducer, methohexital, decreases the effect of the hormone agent, clomifene.
Conjugated Estrogens The enzyme inducer, methohexital, decreases the effect of the hormone agent, conjugated estrogens.
Cyclosporine The barbiturate, methohexital, increases the effect of cyclosporine.
Dexamethasone The barbiturate, methohexital, may decrease the effect of the corticosteroid, dexamethasone.
Diethylstilbestrol The enzyme inducer, methohexital, decreases the effect of the hormone agent, diethylstilbestrol.
Doxycycline The anticonvulsant, methohexital, decreases the effect of doxycycline.
Estradiol The enzyme inducer, methohexital, decreases the effect of the hormone agent, estradiol.
Ethinyl Estradiol This product may cause a slight decrease of contraceptive effect
Felodipine The barbiturate, methohexital, decreases the effect of felodipine.
Fludrocortisone The barbiturate, methohexital, may decrease the effect of the corticosteroid, fludrocortisone.
Folic Acid Folic acid decreases the effect of anticonvulsant, methohexital.
Gefitinib The CYP3A4 inducer, methohexital, may decrease the serum concentration and therapeutic effects of gefitinib.
Griseofulvin The barbiturate, methohexital, decreases the effect of griseofulvin.
Hydrocortisone The barbiturate, methohexital, may decrease the effect of the corticosteroid, hydrocortisone.
Levonorgestrel Phenobarbital decreases the effect of levonorgestrel
Medroxyprogesterone The enzyme inducer, methohexital, decreases the effect of the hormone agent, medroxyprogesterone.
Megestrol The enzyme inducer, methohexital, decreases the effect of the hormone agent, megestrol.
Methadone The barbiturate, methohexital, decreases the effect of methadone.
Metronidazole The barbiturate, methohexital, decreases the effect of metronidazole.
Nifedipine The barbiturate, methohexital, decreases the effect of the calcium channel blocker, nifedipine.
Norethindrone This product may cause a slight decrease of contraceptive effect
Oxtriphylline The barbiturate, methohexital, decreases the effect of oxtriphylline.
Prednisolone The barbiturate, methohexital, may decrease the effect of the corticosteroid, prednisolone.
Prednisone The barbiturate, methohexital, may decrease the effect of the corticosteroid, prednisone.
Quinidine The anticonvulsant, methohexital, decreases the effect of quinidine.
Theophylline The barbiturate, methohexital, decreases the effect of theophylline.
Triamcinolone The barbiturate, methohexital, may decrease the effect of the corticosteroid, triamcinolone.
Trimipramine The barbiturate, Methohexital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Methohexital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Triprolidine The CNS depressants, Triprolidine and Methohexital, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Verapamil Methohexital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Methohexital is initiated, discontinued or dose changed.
Warfarin Methohexital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if methohexital is initiated, discontinued or dose changed.
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
  • 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
  • Koltchine VV, Ye Q, Finn SE, Harrison NL: Chimeric GABAA/glycine receptors: expression and barbiturate pharmacology. Neuropharmacology. 1996;35(9-10):1445-56. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.1943

Predictions


Id Partner name Gene Name Score
523 Gamma-aminobutyric-acid receptor subunit alpha-5 GABRA5 0.0694
423 Gamma-aminobutyric-acid receptor subunit alpha-2 GABRA2 0.0689
580 Gamma-aminobutyric-acid receptor subunit alpha-3 GABRA3 0.0644
530 Gamma-aminobutyric-acid receptor subunit alpha-4 GABRA4 0.0481
841 Gamma-aminobutyric-acid receptor subunit alpha-6 GABRA6 0.0477
6086 Gamma-aminobutyric acid receptor subunit gamma-2 GABRG2 0.0344
4095 Neuronal acetylcholine receptor subunit alpha-7 CHRNA7 0.0323
947 Neuronal acetylcholine receptor subunit alpha-4 CHRNA4 0.0323
918 Glutamate receptor, ionotropic kainate 2 GRIK2 0.0316
921 Glutamate receptor 2 GRIA2 0.031
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.0275
4098 Gamma-aminobutyric-acid receptor subunit beta-1 GABRB1 0.0272
142 Gamma-aminobutyric-acid receptor subunit rho-1 GABRR1 0.0269
6087 Gamma-aminobutyric acid receptor subunit gamma-1 GABRG1 0.026
6093 Gamma-aminobutyric acid receptor subunit delta GABRD 0.0259
6089 Gamma-aminobutyric acid receptor subunit epsilon GABRE 0.0258
4099 Gamma-aminobutyric-acid receptor subunit beta-3 GABRB3 0.0246
6088 Gamma-aminobutyric acid receptor subunit gamma-3 GABRG3 0.0237
6090 Gamma-aminobutyric acid receptor subunit pi GABRP 0.0237
6092 Gamma-aminobutyric acid receptor subunit rho-2 GABRR2 0.0236
6115 Gamma-aminobutyric acid receptor subunit rho-3 GABRR3 0.0236
4512 Cytochrome P450 3A4 CYP3A4 0.0229
811 Translocator protein TSPO 0.019
482 Glycine receptor subunit alpha-1 GLRA1 0.0172
4757 Cytochrome P450 2C9 CYP2C9 0.0163
6013 Cytochrome P450 2E1 CYP2E1 0.0157
240 Gamma-aminobutyric acid type B receptor, subunit 1 GABBR1 0.0151
6091 Gamma-aminobutyric acid receptor subunit theta GABRQ 0.0144
4119 Cytochrome P450 2D6 CYP2D6 0.0142
241 Calcium-transporting ATPase type 2C member 1 ATP2C1 0.0138
6016 Cytochrome P450 2C19 CYP2C19 0.0138
537 ATP synthase delta chain, mitochondrial ATP5D 0.0132
705 Glutamate receptor 1 GRIA1 0.0127
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0124
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0116
6030 Cytochrome P450 2B6 CYP2B6 0.0106
587 Serum albumin ALB 0.0089
3426 Glutamine synthetase glnA 0.0084
3987 Glutamine synthetase GLUL 0.0084
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0072
6107 Cytochrome P450 3A7 CYP3A7 0.007
4209 ATP-sensitive inward rectifier potassium channel 8 KCNJ8 0.0069
4200 Cytochrome P450 1A2 CYP1A2 0.0069
4924 Cytochrome P450 2C8 CYP2C8 0.0066
4118 Cytochrome P450 3A5 CYP3A5 0.0066
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
20 Prostaglandin G/H synthase 1 PTGS1 0.006
5718 Cytochrome P450 2A6 CYP2A6 0.0058
1588 Multidrug resistance protein 1 ABCB1 0.0054
1680 Solute carrier family 2, facilitated glucose transporter member 1 SLC2A1 0.0049
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0047
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
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0042
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0042
556 Alpha-1A adrenergic receptor ADRA1A 0.0042
6024 Cytochrome P450 1A1 CYP1A1 0.0041
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0039
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0037
6020 Aldehyde oxidase AOX1 0.0037
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0034
2981 Phospholipase A2, membrane associated PLA2G2A 0.0033
629 Alpha-2B adrenergic receptor ADRA2B 0.0031
6106 Cytochrome P450 2C18 CYP2C18 0.0031
3811 Cytochrome P450 19A1 CYP19A1 0.003
592 Carbonic anhydrase 4 CA4 0.003
502 5-hydroxytryptamine 2A receptor HTR2A 0.0027
468 Cytochrome P450 4A11 CYP4A11 0.0024
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0023
357 Carbonic anhydrase 2 CA2 0.0021
3937 Fatty-acid amide hydrolase FAAH 0.002
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
444 Alcohol dehydrogenase 1B ADH1B 0.0016
831 D(2) dopamine receptor DRD2 0.0016
103 Muscarinic acetylcholine receptor M1 CHRM1 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
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
276 Sodium- and chloride-dependent GABA transporter 1 SLC6A1 0.0012
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0012
6102 Arylamine N-acetyltransferase 2 NAT2 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
6031 Cytochrome P450 3A43 CYP3A43 0.001
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0009
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0008
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0008
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0007
6144 Solute carrier family 22 member 2 SLC22A2 0.0007
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0006
1898 Cytochrome P450 1B1 CYP1B1 0.0006
776 Bile salt export pump ABCB11 0.0006
6145 Solute carrier family 22 member 1 SLC22A1 0.0006
862 Multidrug resistance-associated protein 1 ABCC1 0.0006
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0005
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