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Phenobarbital chemical structure

IUPAC name
CAS number
ATC code

N05CA24 .

Chemical formula {{{chemical_formula}}}
Molecular weight 232.235 g/mol
Bioavailability >95%
Metabolism Hepatic (mostly CYP2C19)
Elimination half-life 53 to 118 hours
Excretion Renal and fecal
Pregnancy category {{{pregnancy_category}}}
Legal status
Routes of administration Oral, rectal, parenteral (intramuscular and intravenous)

Phenobarbital (INN) or phenobarbitone (former BAN) is a barbiturate, first marketed as Luminal by Bayer. It is the most widely used anticonvulsive drug worldwide [1] and the oldest still commonly used.[2] It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the benzodiazepines for these indications. The World Health Organization recommends its use as first-line for partial and generalized tonic-clonic seizures (those formerly known as Grand Mal) in developing countries. It is a core medicine in the WHO Model List of Essential Medicines, which is a list of minimum medical needs for a basic health care system.[3] In more affluent countries, it is no longer recommended as a first or second-line choice anticonvulsant for most seizure types,[2][4] though it is still commonly used to treat neonatal seizures.

Phenobarbital (and phenobarbital sodium) is manufactured and supplied in various forms: In Tablets of 15, 30, 60 and 100 mg (though not all are available in all countries: for example, in Australia only the 30 mg strength tablets are available); in an oral elixir (commonly 3 mg/mL in strength); and in a form for injection (as phenobarbital sodium - usually 200 mg/mL). The injectable form is used principally to control status epilepticus, while the oral forms are used for prophylactic and maintenance therapy. The dose range for epilepsy is 60–320 mg/day; its very long active half-life means that for some patients, doses do not have to be taken every day, particularly once the dose has been stabilised over a period of several weeks or months and seizures are effectively controlled. It is occasionally still used as a sedative/hypnotic in anxious or agitated patients who may be intolerant of or do not have access to benzodiazepines, neuroleptics and other, newer drugs. For this purpose phenobarbital has a lower dose range - around 30–120 mg/day; however this practice is uncommon in developed countries.[5]


The first barbiturate drug, barbital, was synthesized in 1902 by German chemists Emil Fischer and Joseph von Mering at Bayer. By 1904 several related drugs, including phenobarbital, had been synthesized by Fischer. Phenobarbital was brought to market in 1912 by the drug company Bayer using the brand Luminal. It remained a commonly prescribed sedative and hypnotic until the introduction of benzodiazepines in the 1950s.[6]

Phenobarbital's soporific, sedative and hypnotic properties were well known in 1912, but nobody knew it was also an effective anticonvulsant. The young doctor Alfred Hauptmann[7] gave it to his epilepsy patients as a tranquiliser and discovered that their epileptic attacks were susceptible to the drug. Hauptmann performed a careful study of his patients over an extended period. Most of these patients were using the only effective drug then available, bromide, which had terrible side effects and limited efficacy. On phenobarbital, their epilepsy was much improved: The worst patients suffered fewer and lighter seizures and some patients became seizure free. In addition, they improved physically and mentally as bromides were removed from their regime. Patients who had been institutionalised due to the severity of their epilepsy were able to leave and, in some cases, resume employment. Hauptman dismissed concerns that its effectiveness in stalling epileptic attacks could lead to patients suffering a build-up that needed to be "discharged". As he expected, withdrawal of the drug led to an increase in seizure frequency – it was not a cure. The drug was quickly adopted as the first widely effective anticonvulsant, though World War I delayed its introduction in the U.S.[8]

Between 1934-1945 Phenobarbital, under the brand name Luminal, was used by German doctors under the Nazi party endorsed policy of eugenics to remove children born with disease or deformities from the population so that they would not suffer. Many of the medical staff involved were later to transfer to Nazi hospitals.[9] [10]

Phenobarbital was used to treat neonatal jaundice by increasing liver metabolism and thus lowering bilirubin levels. In the 1950s, phototherapy was discovered, and became the standard treatment.[11]

In 1940, Winthrop Chemical produced sulfathiazole tablets that were contaminated with phenobarbital. This occurred because both tablets were produced side-by-side and equipment could be interchanged. Each antibacterial tablet contained more than twice the required dose of phenobarbital necessary to induce sleep. Hundreds of patients died or were injured as a result. A U.S. Food and Drug Administration investigation was highly critical of Winthrop and the scandal led to the introduction of Good Manufacturing Practice for drugs.[11]

The drug predates the FDA approval processes and has failed to be formally cleared for use in subsequent years. Guidance was issued in June 2006 of plans to enforce US approval for unapproved drugs.[12]

Phenobarbital was used for over 25 years as prophylaxis in the treatment of febrile seizures.[13] Although an effective treatment in preventing recurrent febrile seizures, it had no positive effect on patient outcome or risk of developing epilepsy. The treatment of simple febrile seizures with anticonvulsant prophylaxis is no longer recommended.[14][15]


Phenobarbital is indicated in the treatment of all types of seizures except absence seizures.[4][16] Phenobarbital is no less effective at seizure control than more modern drugs such as phenytoin and carbamazepine. It is, however, significantly less well tolerated.[17][18]

The first line drugs for treatment of status epilepticus are fast acting benzodiazepines such as diazepam or lorazepam. If these fail then phenytoin may be used, with phenobarbital being an alternative in the U.S. but used only third line in the UK.[19] Failing that, the only treatment is anaesthesia in intensive care.[16][20]

Phenobarbital is the first line choice for the treatment of neonatal seizures.[5][21][22] Concerns that neonatal seizures in themselves could be harmful make most physicians treat them aggressively. There is, however, no reliable evidence to support this approach.[23]

Side effects

Sedation and hypnosis are the principal side effects of phenobarbital. Central nervous system effects like dizziness, nystagmus and ataxia are also common. In elderly patients, it may cause excitement and confusion while in children, it may result in paradoxical hyperactivity.

Special precautions

Caution in children. Of anticonvulsant drugs behavioural disturbances occur most frequently with clonazepam and phenobarbital.[24]


Acute intermittent porphyria, oversensitivity for barbiturates, prior dependence on barbiturates, severe respiratory insufficiency and hyperkinesia in children.

Mechanism of Action

See barbiturates.


Poisoning by barbiturates
ICD-10 T423
ICD-9 {{{ICD9}}}
DiseasesDB {{{DiseasesDB}}}
MedlinePlus {{{MedlinePlus}}}
eMedicine med/207
MeSH {{{MeshNumber}}}

Phenobarbital causes a "depression" of the body's systems, mainly the central and peripheral nervous systems; thus, the main characteristic of phenobarbital overdose is a "slowing" of bodily functions, including decreased consciousness (even coma), bradycardia, bradypnea, hypothermia, and hypotension (in massive overdoses). Overdose may also lead to pulmonary edema and acute renal failure as a result of shock.

The electroencephalogram of a person with phenobarbital overdose may show a marked decrease in electrical activity, to the point of mimicking brain death. This is due to profound depression of the central nervous system, and is usually reversible.[25]

Treatment of phenobarbital overdose is supportive, and consists mainly in the maintenance of airway patency (through endotracheal intubation and mechanical ventilation), correction of bradycardia and hypotension (with intravenous fluids and vasopressors, if necessary) and removal of as much drug as possible from the body. Depending on how much time has elapsed since ingestion of the drug, this may be accomplished through gastric lavage (stomach pumping) or use of activated charcoal. Hemodialysis is effective in removing phenobarbital from the body, and may reduce its half-life by up to 90%.[25] There is no specific antidote for barbiturate poisoning.

British veterinarian Donald Sinclair, better known as "Siegfried Farnon" in the "All Creatures Great and Small" books of James Herriot committed suicide at the age of 84 by injecting himself with an overdose of phenobarbital. Activist Abbie Hoffman also committed suicide by consuming phenobarbital, combined with alcohol, on April 12, 1989; the residue of around 150 pills was found in his body at autopsy.[26]


Phenobarbital has an oral bioavailability of approximately 90%. Peak plasma concentrations are reached 8 to 12 hours after oral administration. It is one of the longest-acting barbiturates available – it remains in the body for a very long time (half-life of 2 to 7 days) and has very low protein binding (20 to 45%). Phenobarbital is metabolized by the liver, mainly through hydroxylation and glucuronidation, and induces many isozymes of the cytochrome P450 system. Cytochrome P450 2B6 (CYP2B6) is specifically induced by Phenobarbital via the CAR/RXR nuclear receptor heterodimer. It is excreted primarily by the kidneys.

Veterinary uses

Phenobarbital is one of the initial drugs of choice to treat epilepsy in dogs, and is the initial drug of choice to treat epilepsy in cats.[27]

It may also be used to treat seizures in horses when benzodiazepine treatment has failed or is contraindicated.[28]

Illicit use

The High Incident Bandits used phenobarbital prior to committing the North Hollywood Bank of America robbery.[29]

The Heaven's Gate cult used phenobarbital mixed with vodka to commit a mass suicide in 1997.


  1. Kwan P, Brodie MJ (September 2004). Phenobarbital for the treatment of epilepsy in the 21st century: a critical review. Epilepsia 45 (9): 1141–9.
  2. 2.0 2.1 Phenobarbital. Epilepsy Foundation. URL accessed on 2006-09-07.
  3. (2005). WHO Model List of Essential Medicines. (PDF) World Health Organization. URL accessed on 2006-03-12.
  4. 4.0 4.1 NICE. CG20 Epilepsy in adults and children: NICE guideline. NHS. URL accessed on 2006-09-06.
  5. 5.0 5.1 British Medical Association, Royal Pharmaceutical Society of Great Britain, Royal College of Paediatrics and Child Health and Neonatal and Paediatric Pharmacists Group (2006). "4.8.1 Control of epilepsy" British National Formulary for Children, 255–6, London: BMJ Publishing.
  6. Sneader, Walter (2005-06-23). Drug Discovery, John Wiley and Sons. URL accessed 2006-09-06.
  7. Ole Daniel Enersen. Alfred Hauptmann.
  8. Scott,, Donald F (1993-02-15). The History of Epileptic Therapy, 59–65, Taylor & Francis. URL accessed 2006-09-06.
  9. Marylynne Pitz. A Warhol show explores Germany's Master Race philosophy. Post-Gazette. PG Publishing Co., Inc.. URL accessed on 2007-03-20.
  10. Naomi Schaefer (2004). The Legacy of Nazi Medicine. The New Atlantis, Number 5. URL accessed on 2007-03-20.
  11. 11.0 11.1 Rachel Sheremeta Pepling (June 2005). Phenobarbital. Chemical and Engineering News 83 (25).
  12. Michelle Meadows. The FDA Takes Action Against Unapproved Drugs. FDA Consumer magazine. URL accessed on 2007-09-27.
  13. John M. Pellock, W. Edwin Dodson, Blaise F. D. Bourgeois (2001-01-01). Pediatric Epilepsy, Demos Medical Publishing. URL accessed 2006-09-06.
  14. Robert Baumann. Febrile Seizures. eMedicine. WebMD. URL accessed on 2006-09-06.
  15. various (2005). Diagnosis and management of epilepsies in children and young people. (PDF) Scottish Intercollegiate Guidelines Network. URL accessed on 2006-09-07.
  16. 16.0 16.1 British National Formulary 51
  17. Taylor S, Tudur Smith C, Williamson PR, Marson AG (2003). Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic-clonic seizures. Cochrane Database Systematic Reviews (2): CD002217.
  18. Tudur Smith C, Marson AG, Williamson PR (2003). Carbamazepine versus phenobarbitone monotherapy for epilepsy. Cochrane Database of Systematic Reviews (1): CD001904.
  19. British Medical Association, Royal Pharmaceutical Society of Great Britain, Royal College of Paediatrics and Child Health and Neonatal and Paediatric Pharmacists Group (2006). "4.8.2 Drugs used in status epilepticus" British National Formulary for Children, London: BMJ Publishing.
  20. Kälviäinen R, Eriksson K, Parviainen I (2005). Refractory generalised convulsive status epilepticus : a guide to treatment. CNS Drugs 19 (9): 759–68.
  21. John M. Pellock, W. Edwin Dodson, Blaise F. D. Bourgeois (2001-01-01). Pediatric Epilepsy, Demos Medical Publishing. URL accessed 2006-09-06.
  22. Raj D Sheth. Neonatal Seizures. eMedicine. WebMD. URL accessed on 2006-09-06.
  23. Booth D, Evans DJ (2004). Anticonvulsants for neonates with seizures. Cochrane Database of Systematic Reviews (3): CD004218.
  24. Trimble MR, Cull C (1988). Children of school age: the influence of antiepileptic drugs on behavior and intellect. Epilepsia 29 Suppl 3: S15–9.
  25. 25.0 25.1 Rania Habal. Barbiturate Toxicity. eMedicine. WebMD. URL accessed on 2006-09-14.
  26. includeonly>King, Wayne. "Abbie Hoffman Committed Suicide Using Barbiturates, Autopsy Shows", The New York Times, April 19, 1989. Retrieved on 2008-04-09.
  27. Thomas, WB (2003). "Seizures and narcolepsy" Dewey, Curtis W. (ed.) A Practical Guide to Canine and Feline Neurology, Ames, Iowa: Iowa State Press.
  28. Editor, Cynthia M. Kahn; associate editor Scott Line (February 8, 2005). Kahn, Cynthia M., Line, Scott, Aiello, Susan E. (ed.) The Merck Veterinary Manual, 9th, John Wiley & Sons.
  29. Shootout!: North Hollywood Shootout, History Channel Documentary (last viewed May 11, 2008).

Barbiturates edit

Allobarbital, Amobarbital, Aprobarbital, Barbexaclone, Barbital, Butabarbital, Butalbital, Butobarbital, Cyclobarbital, Ethallobarbital, Heptabarbital, Hexobarbital, Mephobarbital, Metharbital, Methohexital, Methylphenobarbital, Pentobarbital, Phenobarbital, Primidone, Proxibarbal, Reposal, Secobarbital, Talbutal, Thiobarbital, Thiopental, Vinbarbital, Vinylbital

Anticonvulsants edit


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Barbiturates edit

{Phenobarbital} {Methylphenobarbital} {Metharbital} {Barbexaclone}

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