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Identification
NameButabarbital
Accession NumberDB00237  (APRD00752)
Typesmall molecule
Groupsapproved, 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
SynonymLanguageCode
5-Ethyl-5-(1-methylpropyl)-2,4,6(1H,3H,5H)-pyrimidinetrioneNot AvailableNot Available
5-Ethyl-5-(1-methylpropyl)barbituric acidNot AvailableNot Available
5-Sec-butyl-5-ethyl-2,4,6(1H,3H,5H)-pyrimidinetrioneNot AvailableNot Available
5-Sec-butyl-5-ethylbarbituric acidNot AvailableNot Available
5-Sec-butyl-5-ethylpyrimidine-2,4,6(1H,3H,5H)-trioneNot AvailableNot Available
ButabarbitalNot AvailableNot Available
ButisolNot AvailableNot Available
SecbutabarbitalNot AvailableNot Available
Salts
Name/CAS Structure Properties
Butabarbital Sodium
Thumb
  • InChI Key: QORQZMBCPRBCAB-UHFFFAOYNA-M
  • Monoisotopic Mass: 234.098037031
  • Average Mass: 234.2275
DBSALT000312
Brand names
NameCompany
ButalanNot Available
ButisolNot Available
Sarisol No. 2Not Available
Brand mixturesNot Available
Categories
CAS number125-40-6
WeightAverage: 212.2456
Monoisotopic: 212.116092388
Chemical FormulaC10H16N2O3
InChI KeyZRIHAIZYIMGOAB-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassDiazines
SubclassPyrimidines and Pyrimidine Derivatives
Direct parentBarbituric Acid Derivatives
Alternative parentsUreides; Diazinanes; N-unsubstituted Carboxylic Acid Imides; Secondary Carboxylic Acid Amides; Polyamines; Carboxylic Acids
Substituentsureide; 1,3-diazinane; carboxylic acid imide, n-unsubstituted; carboxamide group; secondary carboxylic acid amide; carboxylic acid derivative; polyamine; carboxylic acid; organonitrogen compound
Classification descriptionThis compound belongs to the barbituric acid derivatives. These are compounds containing a perhydropyrimidine ring substituted at C-2, -4 and -6 by oxo groups.
Pharmacology
IndicationFor short-term treatment of insomnia and anxiety disorders
PharmacodynamicsButabarbital, 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 actionButabarbital 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationBarbiturates are metabolized primarily by the hepatic microsomal enzyme system, and most metabolic products are excreted in the urine.
Half lifeNot Available
ClearanceNot Available
ToxicitySigns 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9324
Blood Brain Barrier + 0.9782
Caco-2 permeable - 0.6013
P-glycoprotein substrate Substrate 0.5938
P-glycoprotein inhibitor I Non-inhibitor 0.617
P-glycoprotein inhibitor II Non-inhibitor 0.961
Renal organic cation transporter Non-inhibitor 0.9465
CYP450 2C9 substrate Non-substrate 0.7719
CYP450 2D6 substrate Non-substrate 0.9014
CYP450 3A4 substrate Non-substrate 0.7098
CYP450 1A2 substrate Non-inhibitor 0.8775
CYP450 2C9 substrate Non-inhibitor 0.821
CYP450 2D6 substrate Non-inhibitor 0.933
CYP450 2C19 substrate Non-inhibitor 0.7828
CYP450 3A4 substrate Non-inhibitor 0.9203
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9458
Ames test Non AMES toxic 0.6458
Carcinogenicity Non-carcinogens 0.8533
Biodegradation Not ready biodegradable 0.9759
Rat acute toxicity 3.6803 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.99
hERG inhibition (predictor II) Non-inhibitor 0.9233
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
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Butisol sodium 50 mg tablet2.46USDtablet
Butisol sodium 30 mg tablet1.89USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point166.5 °CPhysProp
water solubility1360 mg/LNot Available
logP1.65WONG,O & MCKEOWN,RH (1988)
Predicted Properties
PropertyValueSource
water solubility1.39e+00 g/lALOGPS
logP1.7ALOGPS
logP1.45ChemAxon
logS-2.2ALOGPS
pKa (strongest acidic)8.48ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count2ChemAxon
polar surface area75.27ChemAxon
rotatable bond count3ChemAxon
refractivity53.4ChemAxon
polarizability21.41ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD03180
KEGG CompoundC07827
PubChem Compound2479
PubChem Substance46505051
ChemSpider2385
ChEBI3228
ChEMBLCHEMBL449
Therapeutic Targets DatabaseDAP000667
PharmGKBPA164743463
Drug Product Database581291
Drugs.comhttp://www.drugs.com/cdi/butabarbital.html
WikipediaButabarbital
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolBarbiturates like butabarbital may increase the metabolism of Vitamin K Antagonists like acenocoumarol. onitor for decreased therapeutic effects of oral anticoagulants if a barbiturate is initiated/dose increased (anticoagulant dosage increases of 30% to 60% may be needed based on monitored PT), or increased effects if a barbiturate is discontinued/dose decreased. An increased frequency of PT monitoring should be considered for the period immediately following barbiturate initiation/dosage changes.
AminophyllineThe barbiturate, butabarbital, decreases the effect of aminophylline.
AmitriptylineBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
AmoxapineBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like amoxipine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
BendamustineDecreases levels of bendamustine by affecting CYP1A2 hepatic enzyme metabolism. May increase concentrations of active metabolites.
BetamethasoneThe barbiturate, butabarbital, may decrease the effect of the corticosteroid, betamethasone.
ClomifeneThe enzyme inducer, butabarbital, decreases the effect of the hormone agent, clomifene.
ClomipramineBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like clomipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Conjugated EstrogensThe enzyme inducer, butabarbital, decreases the effect of the hormone agent, conjugated estrogens.
CyclosporineThe barbiturate, butabarbital, increases the effect of cyclosporine.
DesipramineBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like desipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
DexamethasoneThe barbiturate, butabarbital, may decrease the effect of the corticosteroid, dexamethasone.
DiethylstilbestrolThe enzyme inducer, butabarbital, decreases the effect of the hormone agent, diethylstilbestrol.
Disopyramidearbiturates may increase the metabolism of Disopyramide. Monitor for decreased therapeutic effects of disopyramide if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased.
DoxepinBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like doxepin. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
DoxycyclineThe anticonvulsant, butabarbital, decreases the effect of doxycycline.
DroperidolDroperidol may enhance the CNS depressant effect of CNS Depressants like butabarbital. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.
EltrombopagAffects hepatic CYP1A2 metabolism, will decrease effect/level of eltrombopag. Affects hepatic CYP2C9/10 metabolism, will decrease effect/level of eltrombopag.
EstradiolThe enzyme inducer, butabarbital, decreases the effect of the hormone agent, estradiol.
Ethinyl EstradiolThis product may cause a slight decrease of contraceptive effect
FelodipineThe barbiturate, butabarbital, decreases the effect of felodipine.
FludrocortisoneThe barbiturate, butabarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Folic AcidFolic acid decreases the effect of anticonvulsant, butabarbital.
GefitinibThe CYP3A4 inducer, butabarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
GriseofulvinThe barbiturate, butabarbital, decreases the effect of griseofulvin.
HydrocortisoneThe barbiturate, butabarbital, may decrease the effect of the corticosteroid, hydrocortisone.
HydroxyzineHydroxyzine may enhance the CNS depressant effect of barbiturates like butabarbital. Consider a decrease in the barbiturate dose, as appropriate, when used together with hydroxyzine. With concurrent use, monitor patients closely for excessive response to the combination.
ImipramineBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like imipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
LamotrigineBarbiturates like butabarbital may decrease the serum concentration of lamotrigine. There are separate patient management guidelines for patients age 12 and under and for patients older than 12 years of age. Monitor for decreased serum concentrations/therapeutic effects of lamotrigine if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased.
LevonorgestrelPhenobarbital decreases the effect of levonorgestrel
Medroxyprogesterone AcetateThe enzyme inducer, butabarbital, decreases the effect of the hormone agent, medroxyprogesterone.
Megestrol acetateThe enzyme inducer, butabarbital, decreases the effect of the hormone agent, megestrol.
MethadoneThe barbiturate, butabarbital, decreases the effect of methadone.
MetronidazoleThe barbiturate, butabarbital, decreases the effect of metronidazole.
NifedipineThe barbiturate, butabarbital, decreases the effect of the calcium channel blocker, nifedipine.
NorethindroneThis product may cause a slight decrease of contraceptive effect
NortriptylineBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like nortriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
OxtriphyllineThe barbiturate, butabarbital, decreases the effect of oxtriphylline.
PrednisoloneThe barbiturate, butabarbital, may decrease the effect of the corticosteroid, prednisolone.
PrednisoneThe barbiturate, butabarbital, may decrease the effect of the corticosteroid, prednisone.
ProtriptylineBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like protriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
QuinidineThe anticonvulsant, butabarbital, decreases the effect of quinidine.
TeniposideBarbiturates like butabarbital may decrease the serum concentration of Teniposide. arbiturates may decrease the serum concentration of Teniposide.
TheophyllineThe barbiturate, butabarbital, decreases the effect of theophylline.
TriamcinoloneThe barbiturate, butabarbital, may decrease the effect of the corticosteroid, triamcinolone.
TrimipramineThe barbiturate, Butabarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Butabarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
TriprolidineThe CNS depressants, Triprolidine and Butabarbital, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
VerapamilButabarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Butabarbital is initiated, discontinued or dose changed.
VoriconazoleButabarbital may reduce serum concentrations and efficacy of voriconazole. Concomitant voriconazole and long-acting barbiturates therapy is contraindicated.
WarfarinButabarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if butabarbital is initiated, discontinued or dose changed.
Food InteractionsNot Available

Targets

1. GABA-A receptor (anion channel)

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: positive allosteric modulator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details
Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

References:

  1. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed
  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

2. Neuronal acetylcholine receptor subunit alpha-4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Neuronal acetylcholine receptor subunit alpha-4 P43681 Details

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
  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
  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

3. Neuronal acetylcholine receptor subunit alpha-7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Neuronal acetylcholine receptor subunit alpha-7 P36544 Details

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
  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
  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

4. Glutamate receptor 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor 2 P42262 Details

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
  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

5. Glutamate receptor ionotropic, kainate 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor ionotropic, kainate 2 Q13002 Details

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
  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

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Drug created on June 13, 2005 07:24 / Updated on December 03, 2013 10:09