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Identification
NamePhenobarbital
Accession NumberDB01174  (APRD00184)
Typesmall molecule
Groupsapproved
Description

A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory gamma-aminobutyric acid subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
5-ethyl-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrioneNot AvailableNot Available
5-Ethyl-5-phenyl-pyrimidine-2,4,6-trioneNot AvailableNot Available
5-Ethyl-5-phenylbarbituric acidNot AvailableNot Available
5-ethyl-5-phenylpyrimidine-2,4,6(1H,3H,5H)-trioneNot AvailableNot Available
5-Phenyl-5-ethylbarbituric acidNot AvailableNot Available
PhenobarbitolNot AvailableNot Available
PhenobarbitoneNot AvailableNot Available
Phenobarbituric AcidNot AvailableNot Available
PhenylethylbarbiturateNot AvailableNot Available
Phenylethylbarbituric AcidNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
LuminalNot Available
Brand mixturesNot Available
Categories
CAS number50-06-6
WeightAverage: 232.2353
Monoisotopic: 232.08479226
Chemical FormulaC12H12N2O3
InChI KeyInChIKey=DDBREPKUVSBGFI-UHFFFAOYSA-N
InChI
InChI=1S/C12H12N2O3/c1-2-12(8-6-4-3-5-7-8)9(15)13-11(17)14-10(12)16/h3-7H,2H2,1H3,(H2,13,14,15,16,17)
IUPAC Name
5-ethyl-5-phenyl-1,3-diazinane-2,4,6-trione
SMILES
CCC1(C(=O)NC(=O)NC1=O)C1=CC=CC=C1
Mass Specshow(8.44 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassDiazines
SubclassPyrimidines and Pyrimidine Derivatives
Direct parentBarbituric Acid Derivatives
Alternative parentsUreides; Diazinanes; Benzene and Substituted Derivatives; N-unsubstituted Carboxylic Acid Imides; Secondary Carboxylic Acid Amides; Carboxylic Acids; Polyamines
Substituentsureide; 1,3-diazinane; benzene; 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 the treatment of all types of seizures except absence seizures.
PharmacodynamicsPhenobarbital, the longest-acting barbiturate, is used for its anticonvulsant and sedative-hypnotic properties in the management of all seizure disorders except absence (petit mal).
Mechanism of actionPhenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal.
AbsorptionAbsorbed in varying degrees following oral, rectal or parenteral administration. The salts are more rapidly absorbed than are the acids. The rate of absorption is increased if the sodium salt is ingested as a dilute solution or taken on an empty stomach.
Volume of distributionNot Available
Protein binding20 to 45%
Metabolism

Hepatic (mostly via CYP2C19).

SubstrateEnzymesProduct
Phenobarbital
p-HydroxyphenobarbitalDetails
p-Hydroxyphenobarbital
    Phenobarbital O-sulfateDetails
    p-Hydroxyphenobarbital
      Phenobarbital O-glucuronideDetails
      Route of eliminationNot Available
      Half life53 to 118 hours (mean 79 hours)
      ClearanceNot Available
      ToxicityCNS and respiratory depression which may progress to Cheyne-Stokes respiration, areflexia, constriction of the pupils to a slight degree (though in severe poisoning they may wshow paralytic dilation), oliguria, tachycardia, hypotension, lowered body temperature, and coma. Typical shock syndrome (apnea, circulatory collapse, respiratory arrest, and death) may occur.
      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 + 0.9935
      Blood Brain Barrier + 0.9736
      Caco-2 permeable - 0.5561
      P-glycoprotein substrate Substrate 0.5157
      P-glycoprotein inhibitor I Non-inhibitor 0.6472
      P-glycoprotein inhibitor II Non-inhibitor 0.9869
      Renal organic cation transporter Non-inhibitor 0.9235
      CYP450 2C9 substrate Non-substrate 0.6962
      CYP450 2D6 substrate Non-substrate 0.9116
      CYP450 3A4 substrate Non-substrate 0.7702
      CYP450 1A2 substrate Non-inhibitor 0.84
      CYP450 2C9 substrate Non-inhibitor 0.9023
      CYP450 2D6 substrate Non-inhibitor 0.9593
      CYP450 2C19 substrate Non-inhibitor 0.8664
      CYP450 3A4 substrate Non-inhibitor 0.9236
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9164
      Ames test AMES toxic 0.9107
      Carcinogenicity Non-carcinogens 0.7469
      Biodegradation Not ready biodegradable 0.9894
      Rat acute toxicity 3.1244 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.99
      hERG inhibition (predictor II) Non-inhibitor 0.9354
      Pharmacoeconomics
      ManufacturersNot Available
      Packagers
      Dosage forms
      FormRouteStrength
      ElixirOral
      SolutionIntramuscular
      TabletOral
      Prices
      Unit descriptionCostUnit
      Phenobarbital 130 mg/ml vial4.32USDml
      Phenobarbital 65 mg/ml vial1.63USDml
      Phenobarbital sodium powder0.36USDg
      Pms-Phenobarbital 100 mg Tablet0.15USDtablet
      Phenobarbital powder0.13USDg
      Pms-Phenobarbital 60 mg Tablet0.11USDtablet
      Phenobarbital 97.2 mg tablet0.1USDtablet
      Phenobarbital 64.8 mg tablet0.09USDtablet
      Pms-Phenobarbital 5 mg/ml Elixir0.09USDml
      Phenobarbital 16.2 mg tablet0.08USDtablet
      Phenobarbital 30 mg tablet0.08USDtablet
      Phenobarbital 32.4 mg tablet0.08USDtablet
      Pms-Phenobarbital 30 mg Tablet0.08USDtablet
      Phenobarbital 100 mg tablet0.07USDtablet
      Pms-Phenobarbital 15 mg Tablet0.07USDtablet
      PHENobarbital 20 mg/5ml Elixir0.06USDml
      Phenobarbital 60 mg tablet0.03USDtablet
      Phenobarbital 15 mg tablet0.02USDtablet
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      PatentsNot Available
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point174 °CPhysProp
      water solubility1110 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
      logP1.47HANSCH,C ET AL. (1995)
      pKa7.3BUDAVARI,S ET AL. (1996)
      Predicted Properties
      PropertyValueSource
      water solubility2.76e-01 g/lALOGPS
      logP1.4ALOGPS
      logP1.41ChemAxon
      logS-2.9ALOGPS
      pKa (strongest acidic)8.14ChemAxon
      physiological charge0ChemAxon
      hydrogen acceptor count3ChemAxon
      hydrogen donor count2ChemAxon
      polar surface area75.27ChemAxon
      rotatable bond count2ChemAxon
      refractivity59.75ChemAxon
      polarizability22.61ChemAxon
      number of rings2ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis Reference

      Tong Sun, Shawn Watson, Rajesh Manchanda, “PHENOBARBITAL SALTS; METHODS OF MAKING; AND METHODS OF USE THEREOF.” U.S. Patent US20100035904, issued February 11, 2010.

      US20100035904
      General Reference
      1. Kwan P, Brodie MJ: Phenobarbital for the treatment of epilepsy in the 21st century: a critical review. Epilepsia. 2004 Sep;45(9):1141-9. Pubmed
      2. Taylor S, Tudur Smith C, Williamson PR, Marson AG: Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic-clonic seizures. Cochrane Database Syst Rev. 2001;(4):CD002217. Pubmed
      3. Tudur Smith C, Marson AG, Williamson PR: Carbamazepine versus phenobarbitone monotherapy for epilepsy. Cochrane Database Syst Rev. 2003;(1):CD001904. Pubmed
      4. Kalviainen R, Eriksson K, Parviainen I: Refractory generalised convulsive status epilepticus : a guide to treatment. CNS Drugs. 2005;19(9):759-68. Pubmed
      5. Booth D, Evans DJ: Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004218. Pubmed
      External Links
      ResourceLink
      KEGG DrugD00506
      KEGG CompoundC07434
      PubChem Compound4763
      PubChem Substance46505776
      ChemSpider4599
      ChEBI8069
      ChEMBLCHEMBL40
      Therapeutic Targets DatabaseDAP000061
      PharmGKBPA450911
      IUPHAR2804
      Guide to Pharmacology2804
      Drug Product Database178799
      RxListhttp://www.rxlist.com/cgi/generic/phenbarb.htm
      Drugs.comhttp://www.drugs.com/cdi/phenobarbital.html
      PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/phe1334.shtml
      WikipediaPhenobarbital
      ATC CodesN03AA02
      AHFS Codes
      • 28:24.04
      PDB EntriesNot Available
      FDA labelNot Available
      MSDSshow(53 KB)
      Interactions
      Drug Interactions
      Drug
      AbirateroneStrong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
      AcenocoumarolThe barbiturate, phenobarbital, decreases the anticoagulant effect of acenocoumarol.
      AminophyllineThe barbiturate, phenobarbital, decreases the effect of aminophylline.
      AnisindioneThe barbiturate, phenobarbital, decreases the anticoagulant effect of anisindione.
      AsenapinePhenobarbital is a CYP1A2 inducer and may increase metabolism of asenapine.
      BendamustineIncreases levels of bendamustine by decreasing metabolism. Ethinyl Estradiol is a CYP1A2 inhibitor and concurrent administration may result in elevated plasma concentrations of bendamustine.
      BetamethasoneThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, betamethasone.
      Boceprevir Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
      CabazitaxelConcomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
      CanagliflozinNonselective inducers of UGT enzymes may decrease levels of canagliflozin, thus decreasing efficacy. Consider increase the dose to 300 mg once daily.
      ChlorotrianiseneThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, chlorotrianisene.
      ClomifeneThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, clomifene.
      Conjugated EstrogensThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, conjugated estrogens.
      Cortisone acetateThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, cortisone acetate.
      CyclosporineThe barbiturate, phenobarbital, may decrease the therapeutic effect of cyclosporine by increasing its metabolism.
      DabrafenibStrong CYP3A4 inducers may decrease levels of dabrafenib. Consider alternate therapy.
      DasatinibPhenobarbital may decrease the serum level and efficacy of dasatinib.
      DelavirdineThe anticonvulsant, phenobarbital, decreases the effect of delavirdine.
      DexamethasoneThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, dexamethasone.
      DicoumarolThe barbiturate, phenobarbital, decreases the anticoagulant effect, dicumarol.
      DiethylstilbestrolThe enzyme inducer, phenobarbital, may decrease the therapeutic effect of diethylstilbestrol.
      DisopyramidePhenobarbital decreases levels of disopyramide
      DoxycyclineThe anticonvulsant, phenobarbital, may decrease the therapeutic effect of doxycycline.
      DyphyllineThe barbiturate, phenobarbital, decreases the effect of dyphylline.
      EstradiolThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estradiol.
      Estradiol valerate/DienogestAffects CYP3A4 metabolism, decreases or effects levels of Estradiol valerate/Dienogest.
      EstriolThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estriol.
      EstroneThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estrone.
      EstropipateThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estropipate.
      Ethinyl EstradiolThis product may cause a slight decrease of contraceptive effect
      EtravirineEtravirine, when used concomitantly with phenobarbital, may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy.
      FelbamateFelbamate increases the effect and toxicity of phenobarbital/primidone
      FelodipineThe barbiturate, phenobarbital, decreases the effect of felodipine.
      FludrocortisoneThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
      Folic AcidFolic acid decreases the effect of anticonvulsant, phenobarbital.
      GefitinibThe CYP3A4 inducer, phenobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
      GriseofulvinThe barbiturate, phenobarbital, decreases the effect of griseofulvin.
      HydrocortisoneThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, hydrocortisone.
      ImatinibPhenobarbital decreases levels of imatinib
      ItraconazoleThe barbiturate, phenobarbital, decreases the effect of itraconazole.
      IvacaftorStrong CYP3A4 inducers may decrease levels of ivacaftor. Monitor concomitant therapy closely.
      LevonorgestrelPhenobarbital decreases the effect of levonorgestrel
      Medroxyprogesterone AcetateThe enzyme inducer, phenobarbital, may decrease the effect of the hormone, medroxyprogesterone.
      Megestrol acetateThe enzyme inducer, phenobarbital, may decrease the effect of the hormone, megestrol.
      MestranolThis product may cause a slight decrease of contraceptive effect
      MethadoneThe barbiturate, phenobarbital, decreases the effect of methadone.
      MethoxyfluraneThe barbiturate, phenobarbital, increases the renal toxicity of methoxyflurane.
      MethylprednisoloneThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, methylprednisolone.
      MetoprololThe barbiturate decreases the effect of the metabolized beta-blocker
      MetronidazoleThe barbiturate, phenobarbital, decreases the effect of metronidazole.
      NifedipineThe barbiturate, phenobarbital, may decrease the effect of the calcium channel blocker, nifedipine.
      NorethindroneThis product may cause a slight decrease of contraceptive effect
      OxtriphyllineThe barbiturate, phenobarbital, decreases the effect of oxtriphylline.
      ParamethasoneThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, paramethasone.
      PrednisoloneThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, prednisolone.
      PrednisoneThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, prednisone.
      PropranololThe barbiturate decreases the effect of the metabolized beta-blocker
      QuinestrolThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, quinestrol.
      QuinidineThe anticonvulsant, phenobarbital, decreases the effect of quinidine.
      RegorafenibStrong CYP3A4 inducers may decrease levels of regorafenib.
      RilpivirineStrong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
      RoflumilastAffects CYP3A4 metabolism, decreases level or effect of roflumilast. Also decreases the level or effect of roflumilast by affecting CYP1A2 metabolism.
      RufinamideIncreases clearance of rufinamide thus decreasing plasma concentration of rufinamide.
      SunitinibPossible decrease in sunitinib levels
      TacrolimusPhenobarbital may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Phenobarbital therapy is initiated, discontinued or altered.
      TelithromycinPhenobarbital may decrease the plasma concentration of Telithromycin. Consider alternate therapy.
      TemsirolimusPhenobarbital may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
      TheophyllineThe barbiturate, phenobarbital, decreases the effect of theophylline.
      TiclopidineTiclopidine may decrease the metabolism and clearance of Phenobarbital. Consider alternate therapy or monitor for adverse/toxic effects of Phenobarbital if Ticlopidine is initiated, discontinued or dose changed.
      TipranavirPhenobarbial decreases the concentration of Tipranavir. Monitor for decreased Tipranavir efficacy.
      TramadolPhenobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
      TrazodoneThe CYP3A4 inducer, Phenobarbital, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Phenobarbital is initiated, discontinued or dose changed.
      TretinoinThe strong CYP2C8 inducer, Phenobarbital, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Phenobarbital is initiated, discontinued or dose changed.
      TriamcinoloneThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, triamcinolone.
      TrimipramineThe barbiturate, Phenobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Phenobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
      TriprolidineThe CNS depressants, Triprolidine and Phenobarbital, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
      UlipristalConcomitant therapy with strong CYP3A4 inducers may decrease plasma concentrations of ulipristal and ultimately its effectiveness. Avoid combination therapy.
      VandetanibDecreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
      VemurafenibStrong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
      VerapamilPhenobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Phenobarbital is initiated, discontinued or dose changed.
      VigabatrinVigabatrin reduces serum concentrations of phenobarbital by 8-16%.
      VoriconazolePhenobarbital may reduce serum concentrations and efficacy of voriconazole. Concomitant voriconazole and long-acting barbiturates therapy is contraindicated.
      WarfarinPhenobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if phenobarbital is initiated, discontinued or dose changed.
      Food Interactions
      • Avoid alcohol.
      • Avoid excessive quantities of coffee or tea (Caffeine).
      • Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
      • Take on an empty stomach for quicker absorption

      1. Gamma-aminobutyric acid receptor subunit alpha-1

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

      References:

      1. Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. 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. 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
      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. Macdonald RL, McLean MJ: Anticonvulsant drugs: mechanisms of action. Adv Neurol. 1986;44:713-36. Pubmed
      6. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
      7. 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

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-2 P47869 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. 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

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-3 P34903 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. 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

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-4 P48169 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

      5. Gamma-aminobutyric acid receptor subunit alpha-5

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-5 P31644 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. 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

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 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

      7. 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

      8. 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

      9. 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
      3. Jin LJ, Schlesinger F, Song YP, Dengler R, Krampfl K: The interaction of the neuroprotective compounds riluzole and phenobarbital with AMPA-type glutamate receptors: a patch-clamp study. Pharmacology. 2010;85(1):54-62. doi: 10.1159/000268641. Epub 2009 Dec 23. Pubmed

      10. 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

      1. Cytochrome P450 2C19

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 2C19 P33261 Details

      References:

      1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      2. 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
      3. Madan A, Graham RA, Carroll KM, Mudra DR, Burton LA, Krueger LA, Downey AD, Czerwinski M, Forster J, Ribadeneira MD, Gan LS, LeCluyse EL, Zech K, Robertson P Jr, Koch P, Antonian L, Wagner G, Yu L, Parkinson A: Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab Dispos. 2003 Apr;31(4):421-31. Pubmed

      2. Cytochrome P450 2C9

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 2C9 P11712 Details

      References:

      1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
      2. 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
      3. Kawalek JC, Howard KD, Farrell DE, Derr J, Cope CV, Jackson JD, Myers MJ: Effect of oral administration of low doses of pentobarbital on the induction of cytochrome P450 isoforms and cytochrome P450-mediated reactions in immature Beagles. Am J Vet Res. 2003 Sep;64(9):1167-75. Pubmed

      3. Cytochrome P450 2B6

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 2B6 P20813 Details

      References:

      1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      2. 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

      4. Cytochrome P450 2C8

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 2C8 P10632 Details

      References:

      1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      2. 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
      3. Kawalek JC, Howard KD, Farrell DE, Derr J, Cope CV, Jackson JD, Myers MJ: Effect of oral administration of low doses of pentobarbital on the induction of cytochrome P450 isoforms and cytochrome P450-mediated reactions in immature Beagles. Am J Vet Res. 2003 Sep;64(9):1167-75. Pubmed

      5. Cytochrome P450 3A4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 3A4 P08684 Details

      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
      2. von Bahr C, Steiner E, Koike Y, Gabrielsson J: Time course of enzyme induction in humans: effect of pentobarbital on nortriptyline metabolism. Clin Pharmacol Ther. 1998 Jul;64(1):18-26. Pubmed
      3. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low affinity): implications for interactions with enzyme-inducing drugs. J Clin Pharmacol. 1999 Jun;39(6):567-77. Pubmed

      6. Cytochrome P450 1A2

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 1A2 P05177 Details

      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
      2. Sakuma T, Ohtake M, Katsurayama Y, Jarukamjorn K, Nemoto N: Induction of CYP1A2 by phenobarbital in the livers of aryl hydrocarbon-responsive and -nonresponsive mice. Drug Metab Dispos. 1999 Mar;27(3):379-84. Pubmed

      7. Cytochrome P450 2A6

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 2A6 P11509 Details

      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
      2. Kawalek JC, Howard KD, Farrell DE, Derr J, Cope CV, Jackson JD, Myers MJ: Effect of oral administration of low doses of pentobarbital on the induction of cytochrome P450 isoforms and cytochrome P450-mediated reactions in immature Beagles. Am J Vet Res. 2003 Sep;64(9):1167-75. Pubmed

      8. Cytochrome P450 2E1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 2E1 P05181 Details

      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

      9. Cytochrome P450 3A5

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 3A5 P20815 Details

      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

      10. Cytochrome P450 4A11

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 4A11 Q02928 Details

      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

      11. Cytochrome P450 1A1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 1A1 P04798 Details

      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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. Pubmed

      12. Cytochrome P450 1B1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 1B1 Q16678 Details

      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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. Pubmed

      13. Cytochrome P450 2C18

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 2C18 P33260 Details

      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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. Pubmed

      14. Cytochrome P450 3A7

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 3A7 P24462 Details

      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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. Pubmed

      15. Cytochrome P450 4B1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 4B1 P13584 Details

      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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. Pubmed

      1. Multidrug resistance protein 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inducer

      Components

      Name UniProt ID Details
      Multidrug resistance protein 1 P08183 Details

      References:

      1. Schuetz EG, Beck WT, Schuetz JD: Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol. 1996 Feb;49(2):311-8. Pubmed
      2. Luna-Tortos C, Fedrowitz M, Loscher W: Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008 Dec;55(8):1364-75. Epub 2008 Sep 11. Pubmed

      2. Canalicular multispecific organic anion transporter 2

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Canalicular multispecific organic anion transporter 2 O15438 Details

      References:

      1. Kiuchi Y, Suzuki H, Hirohashi T, Tyson CA, Sugiyama Y: cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett. 1998 Aug 14;433(1-2):149-52. Pubmed
      2. Cherrington NJ, Slitt AL, Maher JM, Zhang XX, Zhang J, Huang W, Wan YJ, Moore DD, Klaassen CD: Induction of multidrug resistance protein 3 (mrp3) in vivo is independent of constitutive androstane receptor. Drug Metab Dispos. 2003 Nov;31(11):1315-9. Pubmed
      3. Slitt AL, Cherrington NJ, Maher JM, Klaassen CD: Induction of multidrug resistance protein 3 in rat liver is associated with altered vectorial excretion of acetaminophen metabolites. Drug Metab Dispos. 2003 Sep;31(9):1176-86. Pubmed
      4. Ogawa K, Suzuki H, Hirohashi T, Ishikawa T, Meier PJ, Hirose K, Akizawa T, Yoshioka M, Sugiyama Y: Characterization of inducible nature of MRP3 in rat liver. Am J Physiol Gastrointest Liver Physiol. 2000 Mar;278(3):G438-46. Pubmed

      3. Bile salt export pump

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Bile salt export pump O95342 Details

      References:

      1. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, Edwards PA: Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem. 2002 Jan 25;277(4):2908-15. Epub 2001 Nov 12. Pubmed

      4. Multidrug resistance-associated protein 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Multidrug resistance-associated protein 1 P33527 Details

      References:

      1. Kiuchi Y, Suzuki H, Hirohashi T, Tyson CA, Sugiyama Y: cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett. 1998 Aug 14;433(1-2):149-52. Pubmed

      5. Solute carrier organic anion transporter family member 2A1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 2A1 Q92959 Details

      References:

      1. Hagenbuch N, Reichel C, Stieger B, Cattori V, Fattinger KE, Landmann L, Meier PJ, Kullak-Ublick GA: Effect of phenobarbital on the expression of bile salt and organic anion transporters of rat liver. J Hepatol. 2001 Jun;34(6):881-7. Pubmed

      6. Canalicular multispecific organic anion transporter 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Canalicular multispecific organic anion transporter 1 Q92887 Details

      References:

      1. Courtois A, Payen L, Le Ferrec E, Scheffer GL, Trinquart Y, Guillouzo A, Fardel O: Differential regulation of multidrug resistance-associated protein 2 (MRP2) and cytochromes P450 2B1/2 and 3A1/2 in phenobarbital-treated hepatocytes. Biochem Pharmacol. 2002 Jan 15;63(2):333-41. Pubmed
      2. Schrenk D, Baus PR, Ermel N, Klein C, Vorderstemann B, Kauffmann HM: Up-regulation of transporters of the MRP family by drugs and toxins. Toxicol Lett. 2001 Mar 31;120(1-3):51-7. Pubmed
      3. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, Edwards PA: Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem. 2002 Jan 25;277(4):2908-15. Epub 2001 Nov 12. Pubmed
      4. Kauffmann HM, Schrenk D: Sequence analysis and functional characterization of the 5’-flanking region of the rat multidrug resistance protein 2 (mrp2) gene. Biochem Biophys Res Commun. 1998 Apr 17;245(2):325-31. Pubmed
      5. Johnson DR, Habeebu SS, Klaassen CD: Increase in bile flow and biliary excretion of glutathione-derived sulfhydryls in rats by drug-metabolizing enzyme inducers is mediated by multidrug resistance protein 2. Toxicol Sci. 2002 Mar;66(1):16-26. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13