Identification

Name
Butabarbital
Accession Number
DB00237  (APRD00752)
Type
Small Molecule
Groups
Approved, Illicit
Description

Butabarbital (trade name Butisol) is a prescription barbiturate sleep aid. Butabarbital has a particularly fast onset of effects and short duration of action compared to other barbiturates, which makes it useful for certain applications such as treating severe insomnia and relieving anxiety before surgical procedures; however it is also relatively dangerous particularly when combined with alcohol, and so is now rarely used, although it is still prescribed in some Eastern European and South American countries. Its short duration of action gives butabarbital a high abuse potential, comparable to secobarbital. [Wikipedia]

Structure
Thumb
Synonyms
  • 5-Ethyl-5-(1-methylpropyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
  • 5-Ethyl-5-(1-methylpropyl)barbituric acid
  • 5-Sec-butyl-5-ethyl-2,4,6(1H,3H,5H)-pyrimidinetrione
  • 5-Sec-butyl-5-ethylbarbituric acid
  • 5-Sec-butyl-5-ethylpyrimidine-2,4,6(1H,3H,5H)-trione
  • Butabarbital
  • Secbutabarbital
Product Ingredients
IngredientUNIICASInChI Key
Butabarbital Sodium9WTD50I918143-81-7QORQZMBCPRBCAB-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Butisol SodiumTablet50 mg/1OralMedPointe Pharmaceuticals2007-08-022007-08-02Us
Butisol SodiumTablet30 mg/1OralMEDA Pharmaceuticals1939-08-012020-01-31Us
Butisol SodiumSolution30 mg/5mLOralMedPointe Pharmaceuticals2007-08-022007-08-02Us
Butisol Sodium Tab 100mgTablet100 mgOralCarter Horner Corp.1982-12-312001-01-02Canada
Butisol Sodium Tab 15mgTablet15 mgOralCarter Horner Corp.1982-12-312001-01-02Canada
Butisol Sodium Tab 30mgTablet30 mgOralCarter Horner Corp.1982-12-312001-01-02Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Phenazopyridine Hydrochloride, Hyoscyamine Hydrobromide, and ButabarbitalButabarbital (15 mg/1) + Hyoscyamine hydrobromide (0.3 mg/1) + Phenazopyridine hydrochloride (150 mg/1)Tablet, coatedOralPhysicians Total Care, Inc.2004-09-032011-06-30Us
Phenazopyridine PlusButabarbital (15 mg/1) + Hyoscyamine hydrobromide (0.3 mg/1) + Phenazopyridine hydrochloride (150 mg/1)Tablet, coatedOralBreckenridge Pharmaceutical, Inc.2005-03-012011-02-28Us
Pyrelle H.B.Butabarbital (15 mg/1) + Hyoscyamine hydrobromide (0.3 mg/1) + Phenazopyridine hydrochloride (150 mg/1)TabletOralAzur Pharma, Inc.2004-01-012010-06-01Us
International/Other Brands
Butalan / Butisol / Sarisol No. 2
Categories
UNII
P0078O25A9
CAS number
125-40-6
Weight
Average: 212.2456
Monoisotopic: 212.116092388
Chemical Formula
C10H16N2O3
InChI Key
ZRIHAIZYIMGOAB-UHFFFAOYSA-N
InChI
InChI=1S/C10H16N2O3/c1-4-6(3)10(5-2)7(13)11-9(15)12-8(10)14/h6H,4-5H2,1-3H3,(H2,11,12,13,14,15)
IUPAC Name
5-(butan-2-yl)-5-ethyl-1,3-diazinane-2,4,6-trione
SMILES
CCC(C)C1(CC)C(=O)NC(=O)NC1=O

Pharmacology

Indication

For short-term treatment of insomnia and anxiety disorders

Associated Conditions
Pharmacodynamics

Butabarbital, 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

Butabarbital 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.

TargetActionsOrganism
AGABA-A receptor (anion channel)
positive allosteric modulator
Human
UNeuronal acetylcholine receptor subunit alpha-4
antagonist
Human
UNeuronal acetylcholine receptor subunit alpha-7
antagonist
Human
UGlutamate receptor 2
antagonist
Human
UGlutamate receptor ionotropic, kainate 2
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Barbiturates are metabolized primarily by the hepatic microsomal enzyme system, and most metabolic products are excreted in the urine.

Half life
Not Available
Clearance
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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Butabarbital can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Butabarbital is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Butabarbital is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Butabarbital is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Butabarbital is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Butabarbital is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Butabarbital is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Butabarbital is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbacavirButabarbital may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseButabarbital may decrease the excretion rate of Acarbose which could result in a higher serum level.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014382
KEGG Drug
D03180
KEGG Compound
C07827
PubChem Compound
2479
PubChem Substance
46505051
ChemSpider
2385
ChEBI
3228
ChEMBL
CHEMBL449
Therapeutic Targets Database
DAP000667
PharmGKB
PA164743463
Drugs.com
Drugs.com Drug Page
Wikipedia
Butabarbital

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Medpointe pharmaceuticals medpointe healthcare inc
  • Alpharma us pharmaceuticals division
  • Wockhardt eu operations (swiss) ag
  • Lannett co inc
  • Meda pharmaceuticals inc
  • Halsey drug co inc
  • Cm bundy co
  • Sandoz inc
  • Solvay pharmaceuticals
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Whiteworth towne paulsen inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Marshall pharmacal corp
  • West ward pharmaceutical corp
Packagers
  • C.O. Truxton Inc.
  • Chattem Chemicals Inc.
  • Meda AB
Dosage forms
FormRouteStrength
SolutionOral30 mg/5mL
TabletOral30 mg/1
TabletOral50 mg/1
TabletOral100 mg
TabletOral15 mg
TabletOral30 mg
Tablet, coatedOral
TabletOral
Prices
Unit descriptionCostUnit
Butisol sodium 50 mg tablet2.46USD tablet
Butisol sodium 30 mg tablet1.89USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)166.5 °CPhysProp
water solubility1360 mg/LNot Available
logP1.65WONG,O & MCKEOWN,RH (1988)
Predicted Properties
PropertyValueSource
Water Solubility1.39 mg/mLALOGPS
logP1.7ALOGPS
logP1.45ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)8.48ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area75.27 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity53.4 m3·mol-1ChemAxon
Polarizability21.41 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9324
Blood Brain Barrier+0.9782
Caco-2 permeable-0.6013
P-glycoprotein substrateSubstrate0.5938
P-glycoprotein inhibitor INon-inhibitor0.617
P-glycoprotein inhibitor IINon-inhibitor0.961
Renal organic cation transporterNon-inhibitor0.9465
CYP450 2C9 substrateNon-substrate0.7719
CYP450 2D6 substrateNon-substrate0.9014
CYP450 3A4 substrateNon-substrate0.7098
CYP450 1A2 substrateNon-inhibitor0.8775
CYP450 2C9 inhibitorNon-inhibitor0.821
CYP450 2D6 inhibitorNon-inhibitor0.933
CYP450 2C19 inhibitorNon-inhibitor0.7828
CYP450 3A4 inhibitorNon-inhibitor0.9203
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9458
Ames testNon AMES toxic0.6458
CarcinogenicityNon-carcinogens0.8533
BiodegradationNot ready biodegradable0.9759
Rat acute toxicity3.6803 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.99
hERG inhibition (predictor II)Non-inhibitor0.9233
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0a4l-6900000000-6e0cbc3d26c5541ad8eb
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot 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:3228)

Targets

Kind
Protein group
Organism
Human
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
  1. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [PubMed:10209232]
  2. 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]
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
  3. 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]
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
  3. 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]
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:37