Pentobarbital

Not to be confused with phenobarbital or sodium pentothal.

Pentobarbital

Systematic (IUPAC) name
5-ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
Clinical data
Trade names	Nembutal
AHFS/Drugs.com	monograph
MedlinePlus	a682416
Pregnancy category	AU: C US: D (Evidence of risk)
Legal status	AU: S8 (Controlled) CA: Schedule IV DE: Anlage III (Prescription only) UK: Class B US: Schedule II UN: Psychotropic Schedule III ℞ (Prescription only)
Routes of administration	Oral, intravenous, intramuscular, rectal; also intraperitoneal & intracardiac (for animal euthanasia)
Pharmacokinetic data
Bioavailability	70-90% oral; 90% rectal
Protein binding	20-45%
Metabolism	Hepatic
Biological half-life	15-48 hours
Excretion	Renal
Identifiers
CAS Number	76-74-4 Y
ATC code	N05CA01 (WHO) QN51AA01 (WHO)
PubChem	CID: 4737
IUPHAR/BPS	5480
DrugBank	DB00312 Y
ChemSpider	4575 Y
UNII	I4744080IR Y
KEGG	D00499 Y
ChEBI	CHEBI:7983 Y
ChEMBL	CHEMBL448 Y
Chemical data
Formula	C11H18N2O3
Molecular mass	226.27
SMILES O=C1NC(=O)NC(=O)C1(C(C)CCC)CC
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) Y Key:WEXRUCMBJFQVBZ-UHFFFAOYSA-N Y
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Pentobarbital (US English) or pentobarbitone (UK English) is a short-acting barbiturate. Pentobarbital can occur as both a free acid and as salts of elements such as sodium and calcium. The free acid is only slightly soluble in water and ethanol.

One brand name for this drug is Nembutal, coined by John S. Lundy, who started using it in 1930, from the structural formula of the sodium salt—Na (sodium) + ethyl + methyl + butyl + al (common suffix for barbiturates). Nembutal is trademarked and manufactured by the Danish pharmaceutical company Lundbeck, and is the only injectable form of pentobarbital approved for sale in the United States.

In high doses, pentobarbital causes death by respiratory arrest. In the United States, the drug has been used for executions of convicted criminals. Lundbeck (one of many manufacturers) does not permit its sale to prisons or corrections departments to carry out the death penalty.

Uses

Medical

Typical applications for pentobarbital are sedative, hypnotic for short term, preanesthetic and control of convulsions in emergencies.

It is also used as a veterinary anesthetic agent.

Pentobarbital also has an application in reducing intracranial pressure in Reye's syndrome, traumatic brain injury and induction of coma in cerebral ischemia patients. Pentobarbital-induced coma has been advocated in patients with acute liver failure refractory to mannitol.

Euthanasia

Pentobarbital can induce death when used in high doses. It is used for euthanasia for humans as well as animals. It is also used by itself, or in combination with complementary agents such as phenytoin, in commercial animal euthanasia injectable solutions.

In the Netherlands, the standard protocol for physician-assisted suicide is intravenously induced thiopental anesthesia, followed by bromide of alcuronium- or pancuronium-induced respiratory arrest. A concentrated oral solution of 100 ml containing 9 grams of pentobarbital sodium along with sugar syrup in a 20% ethanol solution is a standard solution used for self-administration by patient.

The oral dosage of pentobarbital indicated for physician-assisted death in the U.S. states of Oregon, Washington, Vermont, and California (as of January, 2016) is typically 10 g in liquid form. This is considerably higher than the dose for the management of status epilepticus.

Capital punishment

Pentobarbital has been used or considered as a substitute for other drugs traditionally used in the United States for execution when they are in short supply. Such use however is illegal under Danish law, and when this was discovered, after public outcry in Danish media, Lundbeck, the owner of the drug, stopped selling it to US States that practice death penalty. US distributors of the drug are forbidden by the owner to sell it to any customers, such as several state authorities, that practice or participate in executions of humans.

Texas began using pentobarbital for executing death row inmates by lethal injection on July 18, 2012. The use of pentobarbital has been considered by several states, including Ohio, Arizona, Idaho and Washington; those states made the decision to switch following shortages of pancuronium bromide, a muscle relaxant previously used as one component in a three-drug cocktail.

In October 2013, Missouri changed its protocols to allow for a compounded pentobarbital to be used in a lethal dose for executions. On November 20, 2013, Joseph Paul Franklin was executed by the state of Missouri. He was the first inmate executed in three years in the state and the first to die by a single dose of pentobarbital.

Metabolism

Pentobarbital undergoes first-pass metabolism in the liver and possibly the intestines.

Drug interactions

Administration of ethanol, benzodiazepines, opioids, antihistamines, other sedative-hypnotics, and other central nervous system depressants will cause possible additive effects.

Chemistry

Pentobarbital is synthesized by methods analogous to that of amobarbital, the only difference being that the alkylation of α-ethylmalonic ester is carried out with 2-bromopentane (not 1-bromo-3-methylbutane) to give pentobarbital.