A long-acting barbiturate that depresses most metabolic processes at high doses. It is used as a hypnotic and sedative and may induce dependence. Barbital is also used in veterinary practice for central nervous system depression. Barbital is a schedule IV controlled drug.

Structure

Similar Structures

Synonyms

Not Available

Categories

UNII

5WZ53ENE2P

CAS number

57-44-3

Weight

Average: 184.1925
Monoisotopic: 184.08479226

Chemical Formula

C₈H₁₂N₂O₃

InChI Key

FTOAOBMCPZCFFF-UHFFFAOYSA-N

InChI

InChI=1S/C8H12N2O3/c1-3-8(4-2)5(11)9-7(13)10-6(8)12/h3-4H2,1-2H3,(H2,9,10,11,12,13)

IUPAC Name

5,5-diethyl-1,3-diazinane-2,4,6-trione

SMILES

CCC1(CC)C(=O)NC(=O)NC1=O

Pharmacology

Indication

Not Available

Pharmacodynamics

Not Available

Mechanism of action

Target	Actions	Organism
AGamma-aminobutyric acid receptor subunit alpha-1	potentiator	Humans
AGamma-aminobutyric acid receptor subunit alpha-2	potentiator	Humans
AGamma-aminobutyric acid receptor subunit alpha-3	potentiator	Humans
AGamma-aminobutyric acid receptor subunit alpha-4	potentiator	Humans
AGamma-aminobutyric acid receptor subunit alpha-5	potentiator	Humans
AGamma-aminobutyric acid receptor subunit alpha-6	potentiator	Humans
UNeuronal acetylcholine receptor subunit alpha-4	antagonist	Humans
UNeuronal acetylcholine receptor subunit alpha-7	antagonist	Humans
UGlutamate receptor 2	antagonist	Humans
UGlutamate receptor ionotropic, kainate 2	antagonist	Humans

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

Toxicity

Not Available

Affected organisms

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
(R)-warfarin	The metabolism of (R)-warfarin can be increased when combined with Barbital.
(S)-Warfarin	The metabolism of (S)-Warfarin can be increased when combined with Barbital.
1,10-Phenanthroline	The therapeutic efficacy of Barbital can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylthioamphetamine	The risk or severity of adverse effects can be increased when Barbital is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine	The serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be decreased when it is combined with Barbital.
3,5-diiodothyropropionic acid	The metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Barbital.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of adverse effects can be increased when Barbital is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin	The metabolism of 4-hydroxycoumarin can be increased when combined with Barbital.
4-Methoxyamphetamine	The risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Barbital.
5-androstenedione	The metabolism of 5-androstenedione can be increased when combined with Barbital.

Food Interactions

Not Available

References

General References

Not Available

External Links

KEGG Compound: C02517
PubChem Compound: 2294
PubChem Substance: 46508979
ChemSpider: 2206
ChEBI: 31252
ChEMBL: CHEMBL444
Therapeutic Targets Database: DAP001350
PharmGKB: PA448538
Wikipedia: Barbital

ATC Codes

N05CA04 — Barbital

Clinical Trials

Clinical Trials: Not Available

Pharmacoeconomics

Manufacturers: Not Available
Packagers: Not Available
Dosage forms: Not Available
Prices: Not Available
Patents: Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	190 °C	PhysProp
boiling point (°C)	250 °C at 2.20E+01 mm Hg	PhysProp
water solubility	7460 mg/L (at 25 °C)	YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP	0.65	HANSCH,C ET AL. (1995)
logS	-1.39	ADME Research, USCD
pKa	8.14 (at 15 °C)	KORTUM,G ET AL (1961)

Predicted Properties

Property	Value	Source
Water Solubility	3.23 mg/mL	ALOGPS
logP	0.73	ALOGPS
logP	0.72	ChemAxon
logS	-1.8	ALOGPS
pKa (Strongest Acidic)	8.48	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	75.27 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	44.25 m³·mol^-1	ChemAxon
Polarizability	17.59 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	+	0.955
Blood Brain Barrier	+	0.9694
Caco-2 permeable	-	0.6146
P-glycoprotein substrate	Non-substrate	0.5238
P-glycoprotein inhibitor I	Non-inhibitor	0.7826
P-glycoprotein inhibitor II	Non-inhibitor	0.9964
Renal organic cation transporter	Non-inhibitor	0.9395
CYP450 2C9 substrate	Non-substrate	0.7915
CYP450 2D6 substrate	Non-substrate	0.9074
CYP450 3A4 substrate	Non-substrate	0.7823
CYP450 1A2 substrate	Non-inhibitor	0.896
CYP450 2C9 inhibitor	Non-inhibitor	0.9436
CYP450 2D6 inhibitor	Non-inhibitor	0.9586
CYP450 2C19 inhibitor	Non-inhibitor	0.918
CYP450 3A4 inhibitor	Non-inhibitor	0.9723
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9847
Ames test	AMES toxic	0.5531
Carcinogenicity	Non-carcinogens	0.8532
Biodegradation	Not ready biodegradable	0.9462
Rat acute toxicity	3.5489 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9913
hERG inhibition (predictor II)	Non-inhibitor	0.9734

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Download (8.31 KB)

Spectra

Spectrum	Spectrum Type	Splash Key
GC-MS Spectrum - CI-B	GC-MS	splash10-000i-0900000000-90fb45d882d2c3ed038f
GC-MS Spectrum - EI-B	GC-MS	splash10-052f-9400000000-fa1289872f9f35015abc
GC-MS Spectrum - EI-B	GC-MS	splash10-052f-9500000000-856a7fe5dbfd28d00c38
GC-MS Spectrum - EI-B	GC-MS	splash10-0a4l-2900000000-42c0874d0bac13cc2d94
GC-MS Spectrum - EI-B	GC-MS	splash10-0a4u-5900000000-497f9ee367181a6df30a
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

Taxonomy

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: Barbiturate / N-acyl urea / Ureide / 1,3-diazinane / Dicarboximide / Urea / Carbonic acid derivative / Carboxylic acid derivative / Azacycle / Organic nitrogen compound
Molecular Framework: Aliphatic heteromonocyclic compounds
External Descriptors: barbiturates (CHEBI:31252)

Targets

Details1. Gamma-aminobutyric acid receptor subunit alpha-1

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. [PubMed:14579514]
Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [PubMed:10209232]
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:11264449]
Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [PubMed:10487207]

Details2. Gamma-aminobutyric acid receptor subunit alpha-2

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

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:11264449]
Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [PubMed:10209232]

Details3. Gamma-aminobutyric acid receptor subunit alpha-3

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

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:11264449]
Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [PubMed:10209232]

Details4. Gamma-aminobutyric acid receptor subunit alpha-4

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. [PubMed:10209232]

Details5. Gamma-aminobutyric acid receptor subunit alpha-5

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

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:11264449]
Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [PubMed:10209232]

Details6. Gamma-aminobutyric acid receptor subunit alpha-6

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

Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [PubMed:10209232]
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:11264449]

Details7. Neuronal acetylcholine receptor subunit alpha-4

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. [PubMed:11264449]
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:16248797]
Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [PubMed:10487207]

Details8. Neuronal acetylcholine receptor subunit alpha-7

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. [PubMed:11264449]
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:16248797]
Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [PubMed:10487207]

Details9. Glutamate receptor 2

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. [PubMed:11264449]
Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [PubMed:10487207]

Details10. Glutamate receptor ionotropic, kainate 2

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. [PubMed:11264449]
Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [PubMed:10487207]

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Inducer

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Nallani SC, Glauser TA, Hariparsad N, Setchell K, Buckley DJ, Buckley AR, Desai PB: Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane X receptor by topiramate. Epilepsia. 2003 Dec;44(12):1521-8. [PubMed:14636322]

Details2. Cytochrome P450 2C19

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate
Inducer
Curator comments: Barbital is a member of the barbiturate drug class. The majority of drugs in this class induce CYP2C19.

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name: CYP2C19
Uniprot ID: P33261
Uniprot Name: Cytochrome P450 2C19
Molecular Weight: 55930.545 Da

References

Ramirez J, Innocenti F, Schuetz EG, Flockhart DA, Relling MV, Santucci R, Ratain MJ: CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Drug Metab Dispos. 2004 Sep;32(9):930-6. [PubMed:15319333]
Yukawa E, Mamiya K: Effect of CYP2C19 genetic polymorphism on pharmacokinetics of phenytoin and phenobarbital in Japanese epileptic patients using Non-linear Mixed Effects Model approach. J Clin Pharm Ther. 2006 Jun;31(3):275-82. doi: 10.1111/j.1365-2710.2006.00712.x. [PubMed:16789993]
Lee SM, Chung JY, Lee YM, Park MS, Namgung R, Park KI, Lee C: Effects of cytochrome P450 (CYP)2C19 polymorphisms on pharmacokinetics of phenobarbital in neonates and infants with seizures. Arch Dis Child. 2012 Jun;97(6):569-72. doi: 10.1136/archdischild-2011-300538. Epub 2012 Feb 13. [PubMed:22331680]
Hukkanen J: Induction of cytochrome P450 enzymes: a view on human in vivo findings. Expert Rev Clin Pharmacol. 2012 Sep;5(5):569-85. doi: 10.1586/ecp.12.39. [PubMed:23121279]
Ioannides C. (2008). Cytochromes P450. RSC Publishing.
Phenobarbital Monograph [File]

Drug created on July 31, 2007 07:09 / Updated on November 02, 2018 05:01

Barbital

Identification

Structure for Barbital (DB01483)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References

References

References

References

References

References

References

References

Enzymes

References

References