Barbital

From Wikipedia, the free encyclopedia
Barbital
Barbital.svg
Barbital ball-and-stick.png
Clinical data
AHFS/Drugs.com International Drug Names
MedlinePlus a682221
Routes of
administration
Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Biological half-life 30.3 (± 3.2) hours
Identifiers
CAS Number
  • 57-44-3 YesY
PubChem CID
  • 2294
DrugBank
  • DB01483 YesY
ChemSpider
  • 2206 YesY
UNII
  • 5WZ53ENE2P
KEGG
  • D01740 YesY
ChEBI
  • CHEBI:31252 YesY
ChEMBL
  • CHEMBL444 YesY
ECHA InfoCard 100.000.301
Chemical and physical data
Formula C8H12N2O3
Molar mass 184.193 g/mol
3D model (JSmol)
  • Interactive image
  (verify)

Barbital (as known in the United States) or barbitone (as known elsewhere), marketed under the brand names Veronal for the pure acid and Medinal for the sodium salt, was the first commercially available barbiturate. It was used as a sleeping aid (hypnotic) from 1903 until the mid-1950s. The chemical names for barbitone are diethylmalonyl urea or diethylbarbituric acid; hence, the sodium salt (known as medinal, a genericised trademark in the United Kingdom) is known also as sodium diethylbarbiturate.

Synthesis

Barbitone was first synthesized in 1902 by German chemists Emil Fischer and Joseph von Mering, who published their discovery in 1903.[1] Barbitone was prepared by condensing diethylmalonic ester with urea in the presence of sodium ethoxide, and then by adding at least two molar equivalents of ethyl iodide to the silver salt of malonylurea or possibly to a basic solution of the acid. The result was an odorless, slightly bitter, white crystalline powder.

Barbitone can also be synthesized in a condensation reaction from urea and diethyl-2,2-diethylmalonate, a diethyl malonate derivative:

Barbital Synthese.svg

Marketing

Bottle for "Veronal" crystals, named after the Italian city of Verona, was the first commercially available barbiturate, manufactured by Bayer.

Barbitone was marketed in 1904 by the Bayer company as “Veronal”. A soluble salt of barbitone was marketed by the Schering company as “Medinal.” It was dispensed for “insomnia induced by nervous excitability”.[2][unreliable source?] It was provided in either capsules or cachets. The therapeutic dose was ten to fifteen grains (0.65-0.97 grams). 3.5 to 4.4 grams is the deadly dose but sleep has also been prolonged up to ten days with recovery.

Pharmacology

Barbitone was considered to be a great improvement over the existing hypnotics. Its taste was slightly bitter, but better than the strong, unpleasant taste of the commonly used bromides. It had few side effects, and its therapeutic dose was far below the toxic dose. However, prolonged usage resulted in tolerance to the drug, requiring higher doses to reach the desired effect. "I'm literally saturated with it," the Russian tsarina Alexandra Feodeorovna confessed to a friend.[3] Fatal overdoses of this slow-acting hypnotic were not uncommon. Pioneering aviator Arthur Whitten Brown (of "Alcock and Brown" fame) died of an accidental overdose.[4] Japanese writer Ryūnosuke Akutagawa deliberately overdosed on the drug in 1927.

pH buffer

Solutions of sodium barbital have also been used as pH buffers for biological research, e.g., in immunoelectrophoresis or in fixative solutions.[5][6] As barbital is a controlled substance, barbital-based buffers have largely been replaced by other substances.[7]

References

  1. ^ Fischer, Emil; von Mering, Joseph (1903). "Ueber eine neue Klasse von Schlafmitteln". Therapie der Gegenwart. 44: 97–101. 
  2. ^ Finley, Ellingwood (1919). "Veronal". The American Materia Medica, Therapeutics and Pharmacognosy. p. 115. Retrieved 25 July 2015. 
  3. ^ Dehn, Lili The Real Tsaritsa, Boston, Little Brown, 1922, p138
  4. ^ "Arthur Whitten Brown (1886–1948) – Find A Grave Memorial". Findagrave.com. Retrieved 19 April 2014. 
  5. ^ "Wolf D. Kuhlmann, "Buffer Solutions"" (PDF). 10 September 2006. Retrieved 28 July 2014. 
  6. ^ Steven E. Ruzin (1999). Plant Microtechnique and Microscopy. Oxford University Press. Retrieved 28 July 2014. 
  7. ^ Monthony, JF; Wallace, EG; Allen, DM (Oct 1978). "A non-barbital buffer for immunoelectrophoresis and zone electrophoresis in agarose gels". Clinical Chemistry. 24 (10): 1825–7. PMID 568042. 

Further reading

  • (in English) Dombrowski SM, Krishnan R, Witte M, Maitra S, Diesing C, et al. 1998. "Constitutive and barbital-induced expression of the CYP6A2 allele of a high producer strain of CYP6A2 in the genetic background of a low producer strain". Gene 221:69–77.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Barbital&oldid=805792810"
This content was retrieved from Wikipedia : http://en.wikipedia.org/wiki/Barbital
This page is based on the copyrighted Wikipedia article "Barbital"; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA