Identification
- Generic Name
- Metharbital
- DrugBank Accession Number
- DB00463
- Background
Metharbital is a barbiturate anticonvulsant, similar to phenobarbital, marketed as Gemonil by Abbott Laboratories. It was patented in 1905 by Emil Fischer of Merck.
- Type
- Small Molecule
- Groups
- Withdrawn
- Structure
Structure for Metharbital (DB00463)
- Weight
- Average: 198.2191
Monoisotopic: 198.100442324 - Chemical Formula
- C9H14N2O3
- Synonyms
- Metarbital
- Metharbital
- Metharbitalum
Pharmacology
- Indication
Metharbital is used for the treatment of epilepsy.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Metharbital, a barbiturate, is used for the treatment of short term insomnia. It belongs to a group of medicines called central nervous system (CNS) depressants that induce drowsiness and relieve tension or nervousness. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.
- 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.
Target Actions Organism AGamma-aminobutyric acid receptor subunit alpha-2 potentiatorHumans AGamma-aminobutyric acid receptor subunit alpha-3 potentiatorHumans AGamma-aminobutyric acid receptor subunit alpha-4 potentiatorHumans AGamma-aminobutyric acid receptor subunit alpha-5 potentiatorHumans AGamma-aminobutyric acid receptor subunit alpha-6 potentiatorHumans AGABA(A) Receptor positive allosteric modulatorHumans AGamma-aminobutyric acid receptor subunit alpha-1 potentiatorHumans UNeuronal acetylcholine receptor subunit alpha-4 antagonistHumans UNeuronal acetylcholine receptor subunit alpha-7 antagonistHumans UGlutamate receptor 2 antagonistHumans UGlutamate receptor ionotropic, kainate 2 antagonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Metharbital is combined with 1,2-Benzodiazepine. Acetazolamide The risk or severity of adverse effects can be increased when Metharbital is combined with Acetazolamide. Acetophenazine The risk or severity of adverse effects can be increased when Metharbital is combined with Acetophenazine. Aclidinium Metharbital may increase the central nervous system depressant (CNS depressant) activities of Aclidinium. Agomelatine The risk or severity of adverse effects can be increased when Metharbital is combined with Agomelatine. Alfentanil The risk or severity of adverse effects can be increased when Metharbital is combined with Alfentanil. Alimemazine The risk or severity of adverse effects can be increased when Metharbital is combined with Alimemazine. Alloin The therapeutic efficacy of Alloin can be decreased when used in combination with Metharbital. Almotriptan The risk or severity of adverse effects can be increased when Metharbital is combined with Almotriptan. Alosetron The risk or severity of adverse effects can be increased when Metharbital is combined with Alosetron. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Gemonil (Abbott Laboratories)
Categories
- ATC Codes
- N03AA30 — Metharbital
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as barbituric acid derivatives. These are compounds containing a perhydropyrimidine ring substituted at C-2, -4 and -6 by oxo groups.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazines
- Sub Class
- Pyrimidines and pyrimidine derivatives
- Direct Parent
- Barbituric acid derivatives
- Alternative Parents
- N-acyl ureas / Diazinanes / Dicarboximides / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- 1,3-diazinane / Aliphatic heteromonocyclic compound / Azacycle / Barbiturate / Carbonic acid derivative / Carbonyl group / Carboxylic acid derivative / Dicarboximide / Hydrocarbon derivative / N-acyl urea
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 02OS7K758T
- CAS number
- 50-11-3
- InChI Key
- FWJKNZONDWOGMI-UHFFFAOYSA-N
- InChI
- InChI=1S/C9H14N2O3/c1-4-9(5-2)6(12)10-8(14)11(3)7(9)13/h4-5H2,1-3H3,(H,10,12,14)
- IUPAC Name
- 5,5-diethyl-1-methyl-1,3-diazinane-2,4,6-trione
- SMILES
- CCC1(CC)C(=O)NC(=O)N(C)C1=O
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014606
- KEGG Drug
- D01382
- PubChem Compound
- 4099
- PubChem Substance
- 46508167
- ChemSpider
- 3957
- 6825
- ChEBI
- 31827
- ChEMBL
- CHEMBL450
- ZINC
- ZINC000005508997
- Therapeutic Targets Database
- DAP000675
- PharmGKB
- PA164746525
- PDBe Ligand
- VOK
- Wikipedia
- Metharbital
- PDB Entries
- 5stf
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Abbott laboratories pharmaceutical products div
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 150.5 °C PhysProp water solubility 1980 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 1.15 HANSCH,C ET AL. (1995) logS -2.23 ADME Research, USCD pKa 8.01 (at 25 °C) HANSCH,C & LEO,AJ (1985) - Predicted Properties
Property Value Source Water Solubility 19.5 mg/mL ALOGPS logP 1.18 ALOGPS logP 0.94 Chemaxon logS -1 ALOGPS pKa (Strongest Acidic) 7.75 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 66.48 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 49.15 m3·mol-1 Chemaxon Polarizability 19.6 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9716 Blood Brain Barrier + 0.9862 Caco-2 permeable + 0.5234 P-glycoprotein substrate Non-substrate 0.6518 P-glycoprotein inhibitor I Non-inhibitor 0.6178 P-glycoprotein inhibitor II Non-inhibitor 0.95 Renal organic cation transporter Non-inhibitor 0.92 CYP450 2C9 substrate Non-substrate 0.8243 CYP450 2D6 substrate Non-substrate 0.9033 CYP450 3A4 substrate Non-substrate 0.6773 CYP450 1A2 substrate Non-inhibitor 0.8845 CYP450 2C9 inhibitor Non-inhibitor 0.8616 CYP450 2D6 inhibitor Non-inhibitor 0.9379 CYP450 2C19 inhibitor Non-inhibitor 0.8585 CYP450 3A4 inhibitor Non-inhibitor 0.9702 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9834 Ames test Non AMES toxic 0.8918 Carcinogenicity Non-carcinogens 0.8406 Biodegradation Not ready biodegradable 0.8078 Rat acute toxicity 2.8286 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9806 hERG inhibition (predictor II) Non-inhibitor 0.9557
Spectra
- Mass Spec (NIST)
- Download (9.12 KB)
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available GC-MS Spectrum - EI-B GC-MS splash10-00di-8900000000-5c20588bb225d0b4ed7c Mass Spectrum (Electron Ionization) MS splash10-0ab9-5900000000-a7d47fbe125ceae08efb Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name
- GABRA2
- Uniprot ID
- P47869
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-2
- Molecular Weight
- 51325.85 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name
- GABRA3
- Uniprot ID
- P34903
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-3
- Molecular Weight
- 55164.055 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name
- GABRA4
- Uniprot ID
- P48169
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-4
- Molecular Weight
- 61622.645 Da
References
- Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Transporter activity
- Specific Function
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name
- GABRA5
- Uniprot ID
- P31644
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-5
- Molecular Weight
- 52145.645 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name
- GABRA6
- Uniprot ID
- Q16445
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-6
- Molecular Weight
- 51023.69 Da
References
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Positive allosteric modulator
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Components:
References
- ChEMBL Compound Report Card [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
- Gene Name
- GABRA1
- Uniprot ID
- P14867
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-1
- Molecular Weight
- 51801.395 Da
References
- Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. [Article]
- Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [Article]
- 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. [Article]
- Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Ligand-gated ion channel activity
- Specific Function
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeabl...
- Gene Name
- CHRNA4
- Uniprot ID
- P43681
- Uniprot Name
- Neuronal acetylcholine receptor subunit alpha-4
- Molecular Weight
- 69956.47 Da
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. [Article]
- 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. [Article]
- Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Toxic substance binding
- Specific Function
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The cha...
- Gene Name
- CHRNA7
- Uniprot ID
- P36544
- Uniprot Name
- Neuronal acetylcholine receptor subunit alpha-7
- Molecular Weight
- 56448.925 Da
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. [Article]
- 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. [Article]
- Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Ionotropic glutamate receptor activity
- Specific Function
- Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory ne...
- Gene Name
- GRIA2
- Uniprot ID
- P42262
- Uniprot Name
- Glutamate receptor 2
- Molecular Weight
- 98820.32 Da
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. [Article]
- Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Kainate selective glutamate receptor activity
- Specific Function
- Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a co...
- Gene Name
- GRIK2
- Uniprot ID
- Q13002
- Uniprot Name
- Glutamate receptor ionotropic, kainate 2
- Molecular Weight
- 102582.475 Da
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. [Article]
- Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
Drug created at June 13, 2005 13:24 / Updated at May 02, 2022 09:55