Pentobarbital

Pentobarbital

Systematic (IUPAC) name
5-Ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682416
Pregnancy cat.	D (USA)
Legal status	USA: Schedule II (oral and parenteral); Schedule III (rectal), UK: Class B Controlled Substance
Routes	Oral, Intravenous, Intramuscular, Rectal; also Intraperitoneal & Intracardiac (for animal euthanasia)
Pharmacokinetic data
Bioavailability	70-90% oral; 90% rectal
Protein binding	20-45%
Metabolism	Hepatic
Half-life	15-48 hours
Excretion	Renal
Identifiers
CAS number	76-74-4 Y
ATC code	N05CA01 QN51AA01
PubChem	CID 4737
DrugBank	APRD01174
ChemSpider	4575 Y
UNII	I4744080IR Y
KEGG	D00499 Y
ChEBI	CHEBI:7983 Y
ChEMBL	CHEMBL448 Y
Chemical data
Formula	C11H18N2O3
Mol. mass	226.27
SMILES	eMolecules & PubChem
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
N(what is this?)  (verify)

Pentobarbital is a short-acting barbiturate that was first synthesized in 1928. Pentobarbital is available as both a free acid and a sodium salt, the former of which is only slightly soluble in water and ethanol.^[1] One brand name for this drug is Nembutal, coined by Dr. 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).^[2]

Uses

Approved

Pentobarbital's FDA-approved human uses include treatment of seizures and preoperative (and other) sedation; it is also approved as a short-term hypnotic.^[3]

Unapproved / investigational / off-label

Off-label uses of pentobarbital include reduction of intracranial pressure in Reye's syndrome, traumatic brain injury and induction of coma in cerebral ischemia patients.^[3] Pentobarbital-induced coma has been advocated in patients with acute liver failure refractory to mannitol.^[4]

Veterinary medicine

In veterinary medicine, sodium pentobarbital is used as an anaesthetic. It is also used by itself, or in combination with complementary agents such as phenytoin, in commercial animal euthanasia injectable solutions. ^[5]

Human euthanasia

Pentobarbital has also been used for physician-assisted suicide.^{[citation needed]} In the US state of Oregon "oral doses of a barbiturate" have been used for this purpose.^[6]

Also in Switzerland^{[citation needed]} and the Netherlands.^{[citation needed]} It was also used in the Northern Territory of Australia, prior to euthanasia becoming illegal in that region.^{[citation needed]}

Capital punishment

Pentobarbital has been approved or considered for use in executions in various U.S. states.^[7]

The Danish manufacturer of pentobarbital, Lundbeck, expressed displeasure at this use of their product, and on July 1, 2011, announced they would block sales of the drug to U.S. prisons that carry out the death penalty.

Lundbeck is dedicated to saving people’s lives. Use of our products to end lives contradicts everything we are in business to do. Lundbeck is opposed to the use of its product for the purpose of capital punishment.^[8]

They explained this decision with their commitment to UN human rights principles. ^[7]

Metabolism

Pentobarbital undergoes first-pass metabolism in the liver and possibly the intestines.^[9]

Drug interactions

Administration of alcohol, opioids, antihistamines, other sedative-hypnotics, and other central nervous system depressants will cause possible additive effects.^[3]

Recreational use

Pentobarbital is a drug that has been used recreationally.^[10]

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.^[11][12][13]

References

1. ^ "Pentobarbital Compound summary (CID4737)". Pubchem. NCBI. http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4737. 
2. ^ Fosburgh, L. C. (1997). "From this point in time: Some memories of my part in the history of anesthesia--John S. Lundy, MD". AANA journal 65 (4): 323–328. PMID 9281913.  edit
3. ^ ^{a b c} "Pentobarbital". Monograph. AHFS / Drugs.com. http://www.drugs.com/monograph/pentobarbital.html. 
4. ^ Stravitz, R. T.; Kramer, A. H.; Davern, T.; Shaikh, A. O. S.; Caldwell, S. H.; Mehta, R. L.; Blei, A. T.; Fontana, R. J. et al. (2007). "Intensive care of patients with acute liver failure: Recommendations of the U.S. Acute Liver Failure Study Group". Critical Care Medicine 35 (11): 2498–2508. doi:10.1097/01.CCM.0000287592.94554.5F. PMID 17901832.  edit
5. ^ "International". Drugs.com. http://www.drugs.com/international/pentobarbital.html. 
6. ^ "presciption". Death with dignity act - FAQ. Public health Oregon. http://public.health.oregon.gov/ProviderPartnerResources/EvaluationResearch/DeathwithDignityAct/Pages/faqs.aspx#prescription. 
7. ^ ^{a b} "Detailed position (regarding the misuse of pentobarbital)". Lundbeck. http://www.lundbeck.com/global/media/detailed-position. 
8. ^ "Lundbeck's position regarding the misuse of pentobarbital" (Press release). Lundbeck. July 1, 2011. http://www.lundbeck.com/global/media/lundbecks-position-regarding-the-misuse-of-pentobarbital. 
9. ^ Knodell, R. G.; Spector, M. H.; Brooks, D. A.; Keller, F. X.; Kyner, W. T. (1980). "Alterations in pentobarbital pharmacokinetics in response to parenteral and enteral alimentation in the rat". Gastroenterology 79 (6): 1211–1216. PMID 6777235.  edit
10. ^ Griffiths, R. R.; Johnson, M. W. (2005). "Relative abuse liability of hypnotic drugs: A conceptual framework and algorithm for differentiating among compounds" (pdf). The Journal of clinical psychiatry 66 Suppl 9: 31–41. PMID 16336040. http://neuroscience.jhu.edu/griffiths%20papers/v66s0906.pdf.  edit
11. ^ Volwiler, E. H.; Tabern, D. L. (1930). "5,5-SUBSTITUTED BARBITURIC ACIDS". Journal of the American Chemical Society 52 (4): 1676–1679. doi:10.1021/ja01367a061.  edit
12. ^ German imperial patent, D.R.P. 293163 (1916), Bayer
13. ^ GB patent 650354, Wilde, B. E. & Balaban, I. E., "Improvements in the manufacture of substituted barbituric and thiobarbituric acids", issued 1951-02-21, assigned to Geigy 

External links

• Barbiturates on Erowid