Summary: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.

Top Publications

  1. Basic S, Hajnsek S, Bozina N, Filipcic I, Sporis D, Mislov D, et al. The influence of C3435T polymorphism of ABCB1 gene on penetration of phenobarbital across the blood-brain barrier in patients with generalized epilepsy. Seizure. 2008;17:524-30 pubmed publisher
    ..P-glycoprotein (Pgp), a transmembrane transporter encoded by ABCB1 gene and located at the endothelial cells of the blood-brain barrier (BBB), has been associated with epilepsy pharmacoresistance...
  2. Wu X, DUFFEL M, Lehmler H. Oxidation of polychlorinated biphenyls by liver tissue slices from phenobarbital-pretreated mice is congener-specific and atropselective. Chem Res Toxicol. 2013;26:1642-51 pubmed publisher
    ..More 5-OH-PCB 136 was formed in liver tissue slices obtained from animals pretreated with phenobarbital (P450 2B inducer) or, to a lesser extent, dexamethasone (P450 2B and 3A enzyme inducer) compared to tissue ..
  3. van den Broek M, Groenendaal F, Toet M, van Straaten H, van Hasselt J, Huitema A, et al. Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: a thermopharmacological approach. Clin Pharmacokinet. 2012;51:671-9 pubmed
    ..We studied the effect of therapeutic hypothermia on the pharmacokinetics of phenobarbital in asphyxiated neonates, and the clinical efficacy and the effect of phenobarbital on the continuous amplitude-..
  4. Malamiri R, Ghaempanah M, Khosroshahi N, Nikkhah A, Bavarian B, Ashrafi M. Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial. Eur J Paediatr Neurol. 2012;16:536-41 pubmed publisher
    ..Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute ..
  5. Tai S, Yeh C, Phinney K. Development and validation of a reference measurement procedure for certification of phenytoin, phenobarbital, lamotrigine, and topiramate in human serum using isotope-dilution liquid chromatography/tandem mass spectrometry. Anal Bioanal Chem. 2011;401:1915-22 pubmed publisher
    Phenytoin (PHT), phenobarbital (PHB), lamotrigine (LTG), and topiramate (TPM) are some of the most widely used antiepileptic drugs (AEDs). Monitoring of their concentrations in serum is important for the treatment of epilepsy...
  6. Tripoli M, Cordova A, Moschella F. Dupuytren's contracture as result of prolonged administration of phenobarbital. Eur Rev Med Pharmacol Sci. 2011;15:299-302 pubmed
    ..In literature, there are different opinions regarding the phenobarbital, a common antiepileptic drug, and its effective role in the genesis and development of Dupuytren's disease...
  7. Nardou R, Yamamoto S, Chazal G, Bhar A, Ferrand N, Dulac O, et al. Neuronal chloride accumulation and excitatory GABA underlie aggravation of neonatal epileptiform activities by phenobarbital. Brain. 2011;134:987-1002 pubmed publisher
    b>Phenobarbital produces its anti-epileptic actions by increasing the inhibitory drive of γ-aminobutyric acid...
  8. Filippi L, la Marca G, Cavallaro G, Fiorini P, Favelli F, Malvagia S, et al. Phenobarbital for neonatal seizures in hypoxic ischemic encephalopathy: a pharmacokinetic study during whole body hypothermia. Epilepsia. 2011;52:794-801 pubmed publisher
    ..b>Phenobarbital is widely used to treat neonatal seizures, but it is unknown whether its pharmacokinetics is affected by ..
  9. Moore S, Muñana K, Papich M, Nettifee Osborne J. The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital. J Vet Pharmacol Ther. 2011;34:31-4 pubmed publisher
    ..of this study was to determine if the pharmacokinetics of LEV are altered by concurrent administration of phenobarbital (PB). Six healthy dogs received a single oral dose of LEV (16.7-27.8 mg/kg)...

More Information


  1. Konno Y, Kamino H, Moore R, Lih F, Tomer K, Zeldin D, et al. The nuclear receptors constitutive active/androstane receptor and pregnane x receptor activate the Cyp2c55 gene in mouse liver. Drug Metab Dispos. 2010;38:1177-82 pubmed publisher
    ..We have now found that CYP2C55 is induced by phenobarbital (PB) and pregnenolone 16alpha-carbonitrile (PCN) in both mouse kidney and liver...
  2. Jing X, Liu X, Wen T, Xie S, Yao D, Liu X, et al. Combined effects of epileptic seizure and phenobarbital induced overexpression of P-glycoprotein in brain of chemically kindled rats. Br J Pharmacol. 2010;159:1511-22 pubmed publisher, i.p.) for 28 days. Groups were then treated with an oral dose of phenobarbital (45 mg x kg(-1) x day(-1)) for 40 days...
  3. Barks J, Liu Y, Shangguan Y, Silverstein F. Phenobarbital augments hypothermic neuroprotection. Pediatr Res. 2010;67:532-7 pubmed publisher
    ..We hypothesized that early administration of the anticonvulsant phenobarbital after cerebral hypoxia ischemia could enhance the neuroprotective efficacy of delayed-onset hypothermia...
  4. Liang C, Li Y, Xu J, Wang J, Miao X, Tang Y, et al. Enhanced biosynthetic gene expressions and production of ganoderic acids in static liquid culture of Ganoderma lucidum under phenobarbital induction. Appl Microbiol Biotechnol. 2010;86:1367-74 pubmed publisher
    ..In this work, the addition of phenobarbital, a P450 inducer, was used to enhance the production of total and individual ganoderic acids in a two-stage ..
  5. Jin L, Schlesinger F, Song Y, Dengler R, Krampfl K. The interaction of the neuroprotective compounds riluzole and phenobarbital with AMPA-type glutamate receptors: a patch-clamp study. Pharmacology. 2010;85:54-62 pubmed publisher
    ..The aim of the study is to elucidate if there are direct interactions of riluzole and phenobarbital with AMPA-type receptor channels and to determinethe molecular pharmacological mechanisms...
  6. Höcht C, Lazarowski A, Gonzalez N, Mayer M, Opezzo J, Taira C, et al. Differential hippocampal pharmacokinetics of phenobarbital and carbamazepine in repetitive seizures induced by 3-mercaptopropionic acid. Neurosci Lett. 2009;453:54-7 pubmed publisher
    ..The aim of the present work was to assess the involvement of P-glycoprotein in carbamazepine and phenobarbital hippocampal pharmacokinetics in an experimental model of epilepsy, induced by repetitive MP administration...
  7. Mutoh S, Osabe M, Inoue K, Moore R, PEDERSEN L, Perera L, et al. Dephosphorylation of threonine 38 is required for nuclear translocation and activation of human xenobiotic receptor CAR (NR1I3). J Biol Chem. 2009;284:34785-92 pubmed publisher
    ..using an anti-phospho-threonine 38 peptide antibody has, in fact, demonstrated that the classic CAR activator phenobarbital dephosphorylates the corresponding threonine 48 of mouse CAR in the cytoplasm of mouse liver and translocates ..
  8. Raol Y, Lapides D, Keating J, Brooks Kayal A, Cooper E. A KCNQ channel opener for experimental neonatal seizures and status epilepticus. Ann Neurol. 2009;65:326-36 pubmed publisher
    ..We compared the efficacy of flupirtine, a selective KCNQ channel opener, with phenobarbital and diazepam, two drugs in current use for neonatal seizures...
  9. Morra R, Kuruganti S, Lam V, Lucchesi J, Ganguly R. Functional analysis of the cis-acting elements responsible for the induction of the Cyp6a8 and Cyp6g1 genes of Drosophila melanogaster by DDT, phenobarbital and caffeine. Insect Mol Biol. 2010;19:121-30 pubmed publisher
    Many Drosophila cytochrome P450 or Cyp genes are induced by caffeine and phenobarbital (PB)...
  10. Phillips J, Burgoon L, Goodman J. The constitutive active/androstane receptor facilitates unique phenobarbital-induced expression changes of genes involved in key pathways in precancerous liver and liver tumors. Toxicol Sci. 2009;110:319-33 pubmed publisher to elucidate progressive changes, in expression and methylation status, of genes which play key roles in phenobarbital (PB)-induced liver tumorigenesis, with an emphasis on their potential to affect signaling through critical ..
  11. Hayner C, Wuestefeld N, Bolton P. Phenobarbital treatment in a patient with resistant alcohol withdrawal syndrome. Pharmacotherapy. 2009;29:875-8 pubmed publisher
    ..Intravenous phenobarbital was administered in escalating doses of 65 mg followed by 130 mg 15 minutes later, resulting in control of ..
  12. Tamasi V, Juvan P, Beer M, Rozman D, Meyer U. Transcriptional activation of PPARalpha by phenobarbital in the absence of CAR and PXR. Mol Pharm. 2009;6:1573-81 pubmed publisher
    ..nuclear receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor) mediate the effects of phenobarbital on gene transcription...
  13. Shizu R, Shindo S, Yoshida T, Numazawa S. MicroRNA-122 down-regulation is involved in phenobarbital-mediated activation of the constitutive androstane receptor. PLoS ONE. 2012;7:e41291 pubmed publisher
    ..b>Phenobarbital activates CAR, at least in part, in an AMP-activated protein kinase (AMPK)-dependent manner...
  14. Xiao D, Chen Y, Yang D, Yan B. Age-related inducibility of carboxylesterases by the antiepileptic agent phenobarbital and implications in drug metabolism and lipid accumulation. Biochem Pharmacol. 2012;84:232-9 pubmed publisher
    ..test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ..
  15. Boothe D, Dewey C, Carpenter D. Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs. J Am Vet Med Assoc. 2012;240:1073-83 pubmed publisher
    To compare efficacy and safety of treatment with phenobarbital or bromide as the first-choice antiepileptic drug (AED) in dogs. Double-blinded, randomized, parallel, clinical trial. 46 AED-naïve dogs with naturally occurring epilepsy...
  16. Awuah P, Rhieu B, Singh S, Misse A, Monga S. ?-Catenin loss in hepatocytes promotes hepatocellular cancer after diethylnitrosamine and phenobarbital administration to mice. PLoS ONE. 2012;7:e39771 pubmed publisher
    ..Administration of phenobarbital (PB) containing water (0...
  17. Lappin G, Shishikura Y, Jochemsen R, Weaver R, Gesson C, Brian Houston J, et al. Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers. Eur J Pharm Sci. 2011;43:141-50 pubmed publisher
    ..PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the ..
  18. Kwan P, Wang W, Wu J, Li S, Yang H, Ding D, et al. Long-term outcome of phenobarbital treatment for epilepsy in rural China: a prospective cohort study. Epilepsia. 2013;54:537-42 pubmed publisher
    To evaluate the long-term outcome of phenobarbital treatment for convulsive epilepsy in rural China, and to explore factors associated with overall seizure outcomes...
  19. Yasiry Z, Shorvon S. How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years. Epilepsia. 2012;53 Suppl 8:26-39 pubmed publisher
    b>Phenobarbital (phenobarbitone) was first used as an antiepileptic drug 100 years ago, in 1912...
  20. Saito K, Moore R, Negishi M. Nuclear receptor CAR specifically activates the two-pore K+ channel Kcnk1 gene in male mouse livers, which attenuates phenobarbital-induced hepatic hyperplasia. Toxicol Sci. 2013;132:151-61 pubmed publisher
    ..a member of the family of two-pore K(+) ion channels, is specifically induced in the livers of male mice after phenobarbital treatment...
  21. Mutoh S, Sobhany M, Moore R, Perera L, PEDERSEN L, Sueyoshi T, et al. Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling. Sci Signal. 2013;6:ra31 pubmed publisher
    b>Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the ..
  22. Avasiloaiei A, Dimitriu C, Moscalu M, Păduraru L, Stamatin M. High-dose phenobarbital or erythropoietin for the treatment of perinatal asphyxia in term newborns. Pediatr Int. 2013;55:589-93 pubmed publisher
    ..into three groups: one group received supportive treatment; another group received a single dose of 40 mg/kg phenobarbital; and the third received three daily doses of 1000 IU/kg erythropoietin...
  23. Maitre N, Smolinsky C, Slaughter J, Stark A. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. J Perinatol. 2013;33:841-6 pubmed publisher
    Compare neurodevelopment after levetiracetam (LEV) and phenobarbital (PB) for neonatal seizures. Retrospective study of infants who received antiepileptic drugs (AEDs) for neonatal seizures...
  24. Braeuning A, Sanna R, Huelsken J, Schwarz M. Inducibility of drug-metabolizing enzymes by xenobiotics in mice with liver-specific knockout of Ctnnb1. Drug Metab Dispos. 2009;37:1138-45 pubmed publisher
  25. Zhang L, Zeng L, Li Y. Side effects of phenobarbital in epilepsy: a systematic review. Epileptic Disord. 2011;13:349-65 pubmed publisher
    In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects...
  26. Luszczki J, Andres Mach M, Barcicka Klosowska B, Florek Luszczki M, Haratym Maj A, Czuczwar S. Effects of WIN 55,212-2 mesylate (a synthetic cannabinoid) on the protective action of clonazepam, ethosuximide, phenobarbital and valproate against pentylenetetrazole-induced clonic seizures in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:1870-6 pubmed publisher
    ..on the protective action of four classical antiepileptic drugs (AEDs: clonazepam [CZP], ethosuximide [ETS], phenobarbital [PB], and valproate [VPA]) in the mouse pentylenetetrazole (PTZ)-induced clonic seizure model...
  27. Alves L, Hülsmeyer V, Jaggy A, Fischer A, Leeb T, Drogemuller M. Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic Border Collies. J Vet Intern Med. 2011;25:484-9 pubmed publisher
    ..Variation in the ABCB1 gene encoding the permeability-glycoprotein could have an influence on phenobarbital (PB) resistance, which occurs with high frequency in idiopathic epileptic Border Collies (BCs)...
  28. Morita R, Shimamoto K, Ishii Y, Kuwata K, Ogawa B, Imaoka M, et al. Suppressive effect of enzymatically modified isoquercitrin on phenobarbital-induced liver tumor promotion in rats. Arch Toxicol. 2011;85:1475-84 pubmed publisher
    ..the effect of enzymatically modified isoquercitrin (EMIQ) on hepatocellular tumor promotion induced by phenobarbital (PB), male rats were administered a single intraperitoneal injection of 200 mg/kg N-diethylnitrosamine (DEN) ..
  29. Li Y, Buckley D, Wang S, Klaassen C, Zhong X. Genetic polymorphisms in the TATA box and upstream phenobarbital-responsive enhancer module of the UGT1A1 promoter have combined effects on UDP-glucuronosyltransferase 1A1 transcription mediated by constitutive androstane receptor, pregnane X recepto. Drug Metab Dispos. 2009;37:1978-86 pubmed publisher
    ..was to determine whether the genetic polymorphisms in the RNA polymerase II core promoter and the upstream phenobarbital-responsive element module (PBREM) of the UGT1A1 promoter have combined effects on UGT1A1 transcription ..
  30. Siniscalchi A, Gallelli L, Calabrò G, Tolotta G, De Sarro G. Phenobarbital/Lamotrigine coadministration-induced blood dyscrasia in a patient with epilepsy. Ann Pharmacother. 2010;44:2031-4 pubmed publisher
    To report on a patient with epilepsy who developed leukopenia and thrombocytopenia during phenobarbital/lamotrigine treatment.
  31. Rignall B, Braeuning A, Buchmann A, Schwarz M. Tumor formation in liver of conditional ?-catenin-deficient mice exposed to a diethylnitrosamine/phenobarbital tumor promotion regimen. Carcinogenesis. 2011;32:52-7 pubmed publisher
    The antiepileptic drug phenobarbital (PB) is a potent tumor promoter in mouse liver, where it stimulates the selective outgrowth of tumor populations harboring activating mutations in Ctnnb1, encoding ?-catenin...
  32. Lin G, Kozaki T, Scott J. Hormone receptor-like in 96 and Broad-Complex modulate phenobarbital induced transcription of cytochrome P450 CYP6D1 in Drosophila S2 cells. Insect Mol Biol. 2011;20:87-95 pubmed publisher
    b>Phenobarbital (PB) is a prototypical inducer for studies of xenobiotic responses in animals...
  33. Zhang J, Ho T, Callendrello A, Crespi C, Stresser D. A multi-endpoint evaluation of cytochrome P450 1A2, 2B6 and 3A4 induction response in human hepatocyte cultures after treatment with β-naphthoflavone, phenobarbital and rifampicin. Drug Metab Lett. 2010;4:185-94 pubmed
    ..response and time-course for the induction of CYP1A2, CYP2B6 and CYP3A4 by inducing agents β-naphthoflavone, phenobarbital and rifampicin, respectively were examined in two or more donors using multiple end-points (mRNA, enzyme ..
  34. Brandt C, Nozadze M, Heuchert N, Rattka M, Loscher W. Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy. J Neurosci. 2010;30:8602-12 pubmed publisher
    ..The antiepileptic drug phenobarbital, either alone or in combination, was used for comparison...
  35. Zhang C, Kwan P, Zuo Z, Baum L. In vitro concentration dependent transport of phenytoin and phenobarbital, but not ethosuximide, by human P-glycoprotein. Life Sci. 2010;86:899-905 pubmed publisher
    ..transport assays and concentration equilibrium transport assays (CETAs) were performed for phenytoin (PHT), phenobarbital (PB), and ethosuximide (ESM) using wildtype Madin-Darby Canine Kidney II cell line MDCKII and porcine renal ..
  36. Ross J, Plummer S, Rode A, Scheer N, Bower C, Vogel O, et al. Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo. Toxicol Sci. 2010;116:452-66 pubmed publisher
    Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction...
  37. Lachaud A, Auclair Vincent S, Massip L, Audet Walsh E, Lebel M, Anderson A. Werner's syndrome helicase participates in transcription of phenobarbital-inducible CYP2B genes in rat and mouse liver. Biochem Pharmacol. 2010;79:463-70 pubmed publisher
    ..The rat CYP2B2 gene and its closely related mouse homolog, Cyp2b10, are both strongly induced in liver by phenobarbital. We found that there is phenobarbital-dependent recruitment of WRN to the promoter of the CYP2B2 gene as ..
  38. Glykys J, Dzhala V, KUCHIBHOTLA K, Feng G, Kuner T, Augustine G, et al. Differences in cortical versus subcortical GABAergic signaling: a candidate mechanism of electroclinical uncoupling of neonatal seizures. Neuron. 2009;63:657-72 pubmed publisher
    ..Uncoupling increases after treatment with Phenobarbital, which enhances the GABA(A) receptor (GABA(A)R) conductance...
  39. Kojima S, Sasaki J, Tomita M, Saka M, Ishizuka K, Kawakatsu H, et al. Multiple organ toxicity, including hypochromic anemia, following repeated dose oral administration of phenobarbital (PB) in rats. J Toxicol Sci. 2009;34:527-39 pubmed
    A 4-week repeated dose oral toxicity study of phenobarbital (PB) sodium was conducted in F344 rats of both sexes at PB doses of 0.8, 8, and 80 mg/kg/day to fully elucidate its general toxicity including hematological changes...
  40. Dewey C, Cerda Gonzalez S, Levine J, Badgley B, Ducote J, Silver G, et al. Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy. J Am Vet Med Assoc. 2009;235:1442-9 pubmed publisher
    To assess tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with poorly controlled ..