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Identification
Name Pentobarbital
Accession Number DB00312 (APRD01174)
Type small molecule
Groups approved
Description

A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Pentabarbital
Pentabarbitone
Pentobarbital Sodium
Pentobarbitone
Pentobarbiturate
Pentobarbituric acid
Sodium Pentobarbital
Salts Not Available
Brand names
Name Company
Dorsital
Ethaminal
Mebubarbital
Mebumal
Nebralin
Nembutal
Nembutal Sodium
Neodorm
Rivadorm
Brand mixtures
Brand Name Ingredients
Cafergot PB Sup Belladonna + Caffeine + Ergotamine Tartrate + Pentobarbital
Cafergot PB Tab Belladonna + Caffeine + Ergotamine Tartrate + Pentobarbital Sodium
Categories
  • Hypnotics and Sedatives
  • Adjuvants, Anesthesia
  • GABA Modulators
  • Barbiturates
CAS number 76-74-4
Weight Average: 226.2722
Monoisotopic: 226.131742452
Chemical Formula C11H18N2O3
InChI Key InChIKey=WEXRUCMBJFQVBZ-UHFFFAOYSA-N
InChI
InChI=1S/C11H18N2O3/c1-4-6-7(3)11(5-2)8(14)12-10(16)13-9(11)15/h7H,4-6H2,1-3H3,(H2,12,13,14,15,16)
Plain Text
IUPAC Name
5-ethyl-5-(pentan-2-yl)-1,3-diazinane-2,4,6-trione
SMILES
CCCC(C)C1(CC)C(=O)NC(=O)NC1=O
Plain Text
Mass Spec show (7.77 KB)
Taxonomy
Kingdom Organic
Classes
  • Barbiturates
Substructures
  • Barbiturates
  • Carbonyl Compounds
  • Carboxylic Acids and Derivatives
  • Amino Ketones
  • Ureas and Derivatives
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Carboxamides and Derivatives
Pharmacology
Indication For the short-term treatment of insomnia.
Pharmacodynamics Pentobarbital, 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 Pentobarbital 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.
Absorption Barbiturates are absorbed in varying degrees following oral, rectal, or parenteral administration.
Volume of distribution Not Available
Protein binding Not Available
Metabolism by hepatic microsomal enzyme system
Route of elimination Barbiturates are metabolized primarily by the hepatic microsomal enzyme system, and the metabolic products are excreted in the urine, and less commonly, in the feces. Approximately 25 to 50 percent of a dose of aprobarbital or phenobarbital is eliminated unchanged in the urine, whereas the amount of other barbiturates excreted unchanged in the urine is negligible.
Half life 5 to 50 hours (dose dependent)
Clearance Not Available
Toxicity Symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgment, drowsiness or coma, shallow breathing, staggering, and in severe cases coma and death.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ovation pharmaceuticals inc
  • Lannett co inc
  • Vitarine pharmaceuticals inc
  • Whiteworth towne paulsen inc
  • Anabolic inc
  • Elkins sinn div ah robins co inc
  • Everylife
  • Halsey drug co inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Parke davis div warner lambert co
  • L perrigo co
  • Purepac pharmaceutical co
  • Valeant pharmaceuticals international
  • Watson laboratories inc
  • Wyeth ayerst laboratories
  • Lundbeck inc
  • Nexgen pharma inc
Packagers
Dosage forms
Form Route Strength
Solution Intravenous
Prices
Unit description Cost Unit
Pentobarbital sodium powder 27.0 USD g
Nembutal sodium 50 mg/ml via 20.65 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 129.5 °C PhysProp
water solubility 679 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 2.10 HANSCH,C ET AL. (1995)
logS -2.52 ADME Research, USCD
pKa 8.11 (at 25 °C) SERJEANT,EP & DEMPSEY,B (1979)
Predicted Properties
Property Value Source
water solubility 8.64e-01 g/l ALOGPS
logP 2.16 ALOGPS
logP 1.89 ChemAxon
logS -2.4 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 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 58 ChemAxon
polarizability 23.41 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Knodell RG, Spector MH, Brooks DA, Keller FX, Kyner WT: Alterations in pentobarbital pharmacokinetics in response to parenteral and enteral alimentation in the rat. Gastroenterology. 1980 Dec;79(6):1211-6. Pubmed
External Links
Resource Link
KEGG Drug D00499 Link_out
KEGG Compound C07422 Link_out
PubChem Compound 4737 Link_out
PubChem Substance 46508399 Link_out
ChemSpider 4575 Link_out
ChEBI 7983 Link_out
ChEMBL 7983 Link_out
Therapeutic Targets Database DAP000671 Link_out
PharmGKB PA450859 Link_out
Drug Product Database 141690 Link_out
RxList http://www.rxlist.com/cgi/generic2/pentob.htm Link_out
Drugs.com http://www.drugs.com/mtm/pentobarbital.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Pentobarbital Link_out
ATC Codes
  • N05CA01
AHFS Codes
  • 28:24.04
PDB Entries Not Available
FDA label Not Available
MSDS show (50.3 KB)
Interactions
Drug Interactions
Drug Interaction
Aminophylline The barbiturate, pentobarbital, decreases the effect of aminophylline.
Bendamustine Increases levels of bendamustine by decreasing metabolism. Ethinyl Estradiol is a CYP1A2 inhibitor and concurrent administration may result in elevated plasma concentrations of bendamustine.
Betamethasone The barbiturate, pentobarbital, may decrease the effect of the corticosteroid, betamethasone.
Clomifene The enzyme inducer, pentobarbital, decreases the effect of the hormone agent, clomifene.
Conjugated Estrogens The enzyme inducer, pentobarbital, decreases the effect of the hormone agent, conjugated estrogens.
Cyclosporine The barbiturate, pentobarbital, increases the effect of cyclosporine.
Dexamethasone The barbiturate, pentobarbital, may decrease the effect of the corticosteroid, dexamethasone.
Diethylstilbestrol The enzyme inducer, pentobarbital, decreases the effect of the hormone agent, diethylstilbestrol.
Doxycycline The anticonvulsant, pentobarbital, decreases the effect of doxycycline.
Estradiol The enzyme inducer, pentobarbital, decreases the effect of the hormone agent, estradiol.
Estradiol valerate/Dienogest Affects CYP3A4 metabolism, decreases or effects levels of Estradiol valerate/Dienogest.
Ethinyl Estradiol This product may cause a slight decrease of contraceptive effect
Felodipine The barbiturate, pentobarbital, decreases the effect of felodipine.
Fludrocortisone The barbiturate, pentobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Folic Acid Folic acid decreases the effect of anticonvulsant, pentobarbital.
Gefitinib The CYP3A4 inducer, pentobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Griseofulvin The barbiturate, pentobarbital, decreases the effect of griseofulvin.
Hydrocortisone The barbiturate, pentobarbital, may decrease the effect of the corticosteroid, hydrocortisone.
Levonorgestrel Phenobarbital decreases the effect of levonorgestrel
Medroxyprogesterone The enzyme inducer, pentobarbital, decreases the effect of the hormone agent, medroxyprogesterone.
Megestrol The enzyme inducer, pentobarbital, decreases the effect of the hormone agent, megestrol.
Methadone The barbiturate, pentobarbital, decreases the effect of methadone.
Metronidazole The barbiturate, pentobarbital, decreases the effect of metronidazole.
Nifedipine The barbiturate, pentobarbital, decreases the effect of the calcium channel blocker, nifedipine.
Norethindrone This product may cause a slight decrease of contraceptive effect
Oxtriphylline The barbiturate, pentobarbital, decreases the effect of oxtriphylline.
Prednisolone The barbiturate, pentobarbital, may decrease the effect of the corticosteroid, prednisolone.
Prednisone The barbiturate, pentobarbital, may decrease the effect of the corticosteroid, prednisone.
Quinidine The anticonvulsant, pentobarbital, decreases the effect of quinidine.
Telithromycin Pentobarbital may decrease the plasma concentration of Telithromycin. Consider alternate therapy.
Temsirolimus Pentobarbital may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Theophylline The barbiturate, pentobarbital, decreases the effect of theophylline.
Tramadol Pentobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inducer, Pentobarbital, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Pentobarbital is initiated, discontinued or dose changed.
Triamcinolone The barbiturate, pentobarbital, may decrease the effect of the corticosteroid, triamcinolone.
Trimipramine The barbiturate, Pentobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Pentobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Triprolidine The CNS depressants, Triprolidine and Pentobarbital, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Verapamil Pentobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Pentobarbital is initiated, discontinued or dose changed.
Warfarin Pentobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if pentobarbital is initiated, discontinued or dose changed.
Food Interactions Not Available
Targets

1. Gamma-aminobutyric-acid receptor subunit alpha-1

Pharmacological action: yes
Actions: potentiator

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

Organism class: human
UniProt ID: P14867 Link_out
Gene: GABRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Steinbach JH, Akk G: Modulation of GABA receptor channel gating by pentobarbital. J Physiol. 2001 Dec 15;537(Pt 3):715-33. Pubmed
  2. Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. Pubmed
  3. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed
  4. 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. 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
  6. Davies DL, McCauley LD, Bolger MB, Alkana RL: Pressure-sensitive and -insensitive coupling in gamma-aminobutyric acid(A) receptors. Psychopharmacology (Berl). 2001 Oct;157(4):401-10. Pubmed
  7. Rahman M, Zhu D, Lindblad C, Johansson IM, Holmberg E, Isaksson M, Taube M, Backstrom T, Wang MD: GABA-site antagonism and pentobarbital actions do not depend on the alpha-subunit type in the recombinant rat GABA receptor. Acta Physiol (Oxf). 2006 Aug;187(4):479-88. Pubmed
  8. Feigenspan A, Weiler R: Electrophysiological properties of mouse horizontal cell GABAA receptors. J Neurophysiol. 2004 Nov;92(5):2789-801. Epub 2004 Jul 7. Pubmed
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  10. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  11. 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

2. Gamma-aminobutyric-acid receptor subunit alpha-2

Pharmacological action: yes
Actions: potentiator

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

Organism class: human
UniProt ID: P47869 Link_out
Gene: GABRA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. Gamma-aminobutyric-acid receptor subunit alpha-3

Pharmacological action: yes
Actions: potentiator

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

Organism class: human
UniProt ID: P34903 Link_out
Gene: GABRA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

4. Gamma-aminobutyric-acid receptor subunit alpha-4

Pharmacological action: yes
Actions: potentiator

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

Organism class: human
UniProt ID: P48169 Link_out
Gene: GABRA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

5. Gamma-aminobutyric-acid receptor subunit alpha-5

Pharmacological action: yes
Actions: potentiator

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

Organism class: human
UniProt ID: P31644 Link_out
Gene: GABRA5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

6. Gamma-aminobutyric-acid receptor subunit alpha-6

Pharmacological action: yes
Actions: potentiator

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

Organism class: human
UniProt ID: Q16445 Link_out
Gene: GABRA6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

7. Neuronal acetylcholine receptor subunit alpha-4

Pharmacological action: unknown
Actions: antagonist

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

Organism class: human
UniProt ID: P43681 Link_out
Gene: CHRNA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

8. Neuronal acetylcholine receptor subunit alpha-7

Pharmacological action: unknown
Actions: antagonist

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

Organism class: human
UniProt ID: P36544 Link_out
Gene: CHRNA7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

9. Glutamate receptor 2

Pharmacological action: unknown
Actions: antagonist

Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA(quisqualate) > glutamate > kainate

Organism class: human
UniProt ID: P42262 Link_out
Gene: GRIA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

10. Glutamate receptor, ionotropic kainate 2

Pharmacological action: unknown
Actions: antagonist

L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. May be involved in the transmission of light information from the retina to the hypothalamus. This receptor binds domoate > kainate > quisqualate > 6-cyano-7-nitroquinoxaline-2,3-dione > L-glutamate = 6,7- dinitroquinoxaline-2,3-dione > dihydrokainate

Organism class: human
UniProt ID: Q13002 Link_out
Gene: GRIK2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 3A4

Actions: inducer

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

2. Cytochrome P450 2C19

Actions: substrate

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 imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19