pentobarbital
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| common name | pentobarbital | ||||||||||||||||||
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| molecular formula | C11H18N2O3 _ _ _ _ _ _ _ | ||||||||||||||||||
| short description |
colorless to white crystalline powder |
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| molar mass | 226.27 g mol −1 | ||||||||||||||||||
| physical state |
fixed |
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| melting point |
133 °C |
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| pKS value _ _ |
8.11 (25°C) |
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| Wherever possible and customary, SI units are used. Unless otherwise noted, the data given apply under standard conditions . | |||||||||||||||||||
Pentobarbital , as the sodium salt sodium pentobarbital , is a medium-acting barbiturate (derivative of barbituric acid ). It has been used in human medicine as a sleep aid and is still used in veterinary medicine to put people to sleep .
story
In 1915, the Bayer company registered a patent for this substance.
acquisition and presentation
Pentobarbital is a naturally occurring , synthetically produced derivative of barbituric acid that can be prepared by reacting urea with an appropriately alkylated diethyl malonate , in this case diethyl 2-ethyl-2-(1-methyl-butyl)-malonate:
Due to the oxygen bonded to the C2 atom, pentobarbital belongs to the oxybarbiturates, its thio analogue is thiopental . Pentobarbital is also formed in the body as a breakdown product of thiopental.
properties
Physical Properties
Pentobarbital has an optically active center, which means there is an ( R ) form and an ( S ) form that relate to each other like an image and a mirror image. The angle of rotation for the plane of polarized light ( sodium D lamp) of the ( S ) form is α 20 = −13.19°, that of the ( R ) form α 20 = +13.13°.
stereochemistry
In its synthesis, however, pentobarbital is always initially obtained as a racemate , i.e. a 1:1 mixture of both enantiomers . However, the importance of the enantiomeric purity of synthetically produced active ingredients has meanwhile become an important criterion in drug provings, since the two enantiomers of a chiral drug almost always show different pharmacology and pharmacokinetics, which was often ignored in the past due to a lack of knowledge about stereochemical relationships.
polymorphism
Pentobarbital has two polymorphs; Form I (melting point: 115 °C) can be converted to form II, which has a higher melting point, when heated to 110 °C. Both forms differ significantly in oral bioavailability. Form I has a much higher bioavailability than Form II.
safety instructions
Pentobarbital acts as a hypnotic (sleeping pill) when dosed in the milligram range, but can be fatal in higher doses. The lethal dose for humans is in the range of a few grams, depending on body weight.
analytics
The reliable qualitative and quantitative determination of pentobarbital is possible after appropriate sample preparation by coupling HPLC with mass spectrometry
use
In human medicine
Pentobarbital was once used as a sleep aid, similar to heptabarbital , cyclobarbital , and aprobarbital , for example. The median dose was between 100 and 200 mg. The substance can lead to psychological and physical dependence. Sudden discontinuation of the drug can lead to delirium tremens , especially with higher doses – similar to alcoholism . Barbiturate addicts need to withdraw slowly because abrupt withdrawal can lead to seizures and collapse. In an overdose, pentobarbital paralyzes the respiratory center and causes death by asphyxiation .
Today, pentobarbital is no longer used as a sleep aid. Due to the risks and side effects described, it is only used in human medicine after strict indications have been made and other measures in the field of treatment and seizure prophylaxis of epileptic seizures have been exhausted .
As a means of killing
Active euthanasia and suicide
Some euthanasia organizations such as B. Exit or Dignitas , pentobarbital is used to induce death by falling asleep and suffocation. In Switzerland, this drug can in principle be prescribed by any doctor, but so far only very few pharmacies are willing to procure it - even though the cantonal pharmacists have issued guidelines on this. In Germany, the prescription of a drug for the purpose of suicide was prohibited until the Federal Constitutional Court ruled to the contrary on February 26, 2020, but the Federal Administrative Court ruled in March 2017 that exceptions must be made for the seriously and incurably ill in extreme cases. Even after the judgment of the Federal Constitutional Court, the Federal Institute for Drugs and Medical Devices rejected all applications on Jens Spahn's instructions . In February 2022, the Higher Administrative Court of Münster opposed the case law of the Federal Administrative Court and rejected the lawsuits of three seriously ill people who had applied to the Federal Institute for Drugs for access to pentobarbital.
executions
On December 16, 2010, according to media reports, pentobarbital was allegedly used for the first time in the USA as the sole means of carrying out the death penalty by lethal injection , although it has already been described in the relevant literature as a common drug for execution purposes in the USA. In a July 17, 2012 press release, the Georgia Department of Corrections announced it was changing its method of execution from a poisonous cocktail of three sequentially administered chemicals to using pentobarbital as the sole chemical. The postponement of the controversial execution of mentally handicapped convict Warren Lee Hill to July 23, 2012 was justified with the conversion of the execution method to pentobarbital.
euthanasia of animals
In veterinary medicine, pentobarbital is used to painlessly and safely euthanize large and small animals by intravenous or intraperitoneal injection , using the water-soluble sodium salt (pentobarbital sodium). The animals quickly fall into a deep sleep, which in the case of the same temperature quickly, painlessly and without reflexes and without significant excitations passes into death through cardiac and respiratory arrest.
In Switzerland, pentobarbital may not be used in animals used for food production. Food-producing animals cannot be treated with pentobarbital in the EU; the meat of animals euthanized with pentobarbital may not be released for consumption.
trade names
- Human medicine: Nembutal (USA)
- Veterinary: Eutha (D), Euthadorm (D), Euthanimal (D), Euthoxin (D), Exagon (D), Narcoren (D), Narkodorm (D), Release (D)
itemizations
- ↑ a b c entry on pentobarbital. In: Rompp Online . Georg Thieme Verlag, accessed November 12, 2014.
- ↑ Pentobarbital sodium external identifiers or database links : CAS number:57-33-0 , EC number: 200-323-9, ECHA -InfoCard: 100.000.294 , GESTIS substance database : 100181 , PubChem : 23676152 , ChemSpider : 5762 , Wikidata : Q27107638 .
- ↑ a b c Pentobarbital entry in the ChemIDplus database of the United States National Library of Medicine (NLM)
- ↑ a b Data sheet pentobarbital at Sigma-Aldrich , retrieved November 10, 2021 ( PDF ).
- ↑ Patent application DE293163A : Process for the production of derivatives of barbituric acid. Filed February 12, 1915 , published July 15, 1916 , applicant: Farbenfabriken vorm. Friedr. Bayer & Co.
- ↑ EJ Ariëns: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology . In: European Journal of Clinical Pharmacology . tape 26 , no. 6 , November 1984, p. 663-668 , doi : 10.1007/BF00541922 .
- ↑ JEF Reynolds, AB Prasad (eds.): Martindale-The Extra Pharmacopoeia. 28th edition. The Pharmaceutical Press, London 1982, p. 810.
- ↑ Draguet-Brughmans M, Bouche R, Flandre JP, Van den Bulcke A: Polymorphism and bioavailability of pentobarbital . tape 54 , no. 5 , 1979, p. 140-145 .
- ↑ Tian H, Zhou X, Chen C, He Y, Yu H, Zheng X: Simultaneous Determination of Phenobarbital, Pentobarbital, Amobarbital and Secobarbital in Raw Milk via Liquid Chromatography with Electron Spray Ionization Tandem Mass Spectrometry. In: Korean J Food Sci Anim Resource. Vol. 37, No. 6, 2017, pp. 847–854. PMID 29725206
- ↑ Zhang X, Lin Z, Li J, Huang Z, Rao Y, Liang H, Yan J, Zheng F: Rapid determination of nine barbiturates in human whole blood by liquid chromatography-tandem mass spectrometry. In: Drug Test Anal. Vol 9, No 4, Apr 2017, pp 588-595. PMID 27368111
- ↑ Hans-Martin Grünig, Christian Robert / Kantonsapothekervereinigung: Position paper: Dispensing pentobarbital sodium for euthanasia. (PDF) (No longer available online.) Archived from the original on 2016-03-24 ; retrieved April 13, 2018 .
- ↑ Kolja Schwarz: Help for suicide must not be prohibited. In: daily news . February 26, 2020.
- ↑ Ludwig A. Minelli: There are still judges in Germany. hpd , March 6, 2017, retrieved April 20, 2018 .
- ↑ Judgment of March 2, 2017, BVerwG 3 C 19.15 .
- ↑ No claim for poison from the state. In: faz.net. Retrieved February 2, 2022 .
- ↑ US prisoner executed with animal anesthetic. In: Mirror online. December 17, 2010.
- ↑ Stephen Trombley, The Execution Protocol. Inside America's Capital Punishment Industry. Crown, NY 1992.
- ↑ Georgia Department of Corrections: Corrections to Change Execution Protocol. ( Memento of 25 August 2012 at the Internet Archive ) press release. July 17, 2012.
- ↑ Pentobarbital entry at Vetpharm, retrieved December 3, 2011.
- ↑ W. Loescher, A. Richter, H. Potschka (eds.): Pharmacotherapy in pets and livestock. Founded by W. Loescher, FR Unbemach and R. Kroker. Georg Thieme Verlag, 2014, p. 163 f.
- ↑ BfArM database, retrieved on December 1, 2020.
