Barbital (or barbitone), 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 barbital 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.
Barbital, then called "Veronal", was first synthesized in 1902 by German chemists Emil Fischer and Joseph von Mering, who published their discovery in 1903.[1] Barbital was prepared by condensing diethylmalonic ester with urea in the presence of sodium ethoxide, or by adding at least two molar equivalents of ethyl iodide to the silver salt of malonylurea (barbituric acid) or possibly to a basic solution of the acid. The result was an odorless, slightly bitter, white crystalline powder.[2]
Its introduction followed the investigations of Fischer and von Mering on the pharmacological properties of certain open and closed acylureas (then called ureides). Led by the impression that hypnotic action appears to be largely dependent on the presence of ethyl groups, they prepared diethylacetyl urea, diethylmalonyl urea (i.e., Barbital itself), and dipropylmalonyl urea. All three were found to be hypnotics: the first was about equal in power to the already-known sulphonal (now sulfonmethane), whilst the third was four times as powerful, but its use was attended by prolonged after-effects. Veronal was found to be midway.[2]
Bottle for "Veronal" crystals, named after the Italian city of Verona, was the first commercially available barbiturate, manufactured by Bayer.
Barbital was marketed in 1904 by the Bayer company as “Veronal”. A soluble salt of barbital was marketed by the Schering company as “Medinal.” It was dispensed for “insomnia induced by nervous excitability”.[3][unreliable source?] It was provided in either crystal form or in cachets (capsules). The therapeutic dose was ten to fifteen grains (0.6-1 grams). 3.5 to 4.4 grams (55 to 68 grains) is the deadly dose but sleep has also been prolonged up to ten days with recovery.
Pharmacology
Barbital 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 Feodorovna confessed to a friend.[4] Fatal overdoses of this slow-acting hypnotic were not uncommon. Pioneering aviator Arthur Whitten Brown (of "Transatlantic flight of Alcock and Brown" fame) died of an accidental overdose.
A photoswitchable derivative of barbital based on a donor-acceptor Stenhouse adduct (DASA) has been developed for research purposes (photopharmacology). DASA-barbital shows neuronal activity via GABAA receptors and reversible photoisomerization in water using cyclodextrin.[5]
pH buffer
Solutions of sodium barbital have also been used as pH buffers for biological research, e.g., in immunoelectrophoresis or in fixative solutions.[6][7] As barbital is a controlled substance, barbital-based buffers have largely been replaced by other substances.[8]
In the D. H. Lawrence story, The Lovely Lady, the titular character dies from a self-administered overdose.[13]
Barbital, under the name of "Veronal", has been used as a plot device in the author Agatha Christie's murder mysteries.[14]
In Stephen King's "The Stand", some characters used Veronal in small doses as a way to suppress the ever-intensifying nightmares involving the "dark man" they communally experienced.
The main character in Dorothy Parker's short story Big Blonde, Hazel Morse, buys 2 bottles of Veronal tablets over the counter with the intention of committing suicide.
In Miroslav Krleža's drama "Messrs. Glembay", Irena Danielli-Basilides overdosed on Veronal as her third and fatal suicide attempt.
References
^Fischer E, von Mering J (1903). "Ueber eine neue Klasse von Schlafmitteln" [About a new class of sleeping pills]. Therapie der Gegenwart (in German). 44: 97–101.
^ abOne or more of the preceding sentences incorporates text from a publication now in the public domain: Chisholm, Hugh, ed. (1911). "Veronal". Encyclopædia Britannica. Vol. 27 (11th ed.). Cambridge University Press. p. 1037.
^Finley E (1919). "Veronal". The American Materia Medica, Therapeutics and Pharmacognosy. p. 115. Retrieved 25 July 2015.
^Dehn L (1922). The Real Tsaritsa. Boston: Little Brown. p. 138.
^Castagna, Rossella; Maleeva, Galyna; Pirovano, Deborah; Matera, Carlo; Gorostiza, Pau (2022-08-17). "Donor–Acceptor Stenhouse Adduct Displaying Reversible Photoswitching in Water and Neuronal Activity". Journal of the American Chemical Society. 144 (34): 15595–15602. doi:10.1021/jacs.2c04920. ISSN 0002-7863. PMID 35976640. S2CID 251623598.
^Kuhlmann WD (10 September 2006). (PDF). Archived from the original (PDF) on 9 November 2016. Retrieved 28 July 2014.
^Ruzin SE (1999). . Oxford University Press. Archived from the original on 3 June 2019. Retrieved 28 July 2014.
^Monthony JF, Wallace EG, Allen DM (October 1978). "A non-barbital buffer for immunoelectrophoresis and zone electrophoresis in agarose gels". Clinical Chemistry. 24 (10): 1825–7. doi:10.1093/clinchem/24.10.1825. PMID 568042.
^Le Matin (in French), 1942-07-06, retrieved 2022-06-04
^I Will Bear Witness by Victor Klemperer (Author), Martin Chalmers (Translator) 1998
^Cargas, Harry J. (1999). Problems Unique to the Holocaust. Univ Pr of Kentucky. p. 44. ISBN9780813121017.
^. 2008-06-10. Archived from the original on 2008-06-10. Retrieved 2021-07-08.
^Lawrence, D. H. (David Herbert) (1988). The virgin and the gypsy : and other stories. Internet Archive. London : Marshall Cavendish. ISBN978-0-86307-694-7.
^"A quote from The Murder of Roger Ackroyd". www.goodreads.com. Retrieved 2021-10-22.
Further reading
Dombrowski SM, Krishnan R, Witte M, Maitra S, Diesing C, Waters LC, Ganguly R (October 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 (1): 69–77. doi:10.1016/s0378-1119(98)00436-3. PMID 9852951.
Norena Shopland T he Veronal Mystery (Wordcatcher Publishing) 2020
January 07, 2023
barbital, barbitone, marketed, under, brand, names, veronal, pure, acid, medinal, sodium, salt, first, commercially, available, barbiturate, used, sleeping, hypnotic, from, 1903, until, 1950s, chemical, names, barbital, diethylmalonyl, urea, diethylbarbituric,. Barbital or barbitone 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 barbital 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 BarbitalClinical dataTrade namesVeronal MedinalAHFS Drugs comInternational Drug NamesMedlinePlusa682221Routes ofadministrationOralATC codeN05CA04 WHO Legal statusLegal statusCA Schedule IV DE Anlage III Special prescription form required US Schedule IVPharmacokinetic dataElimination half life30 3 3 2 hoursIdentifiersIUPAC name 5 5 diethylpyrimidine 2 4 6 1H 3H 5H trioneCAS Number57 44 3 YPubChem CID2294DrugBankDB01483 YChemSpider2206 YUNII5WZ53ENE2PKEGGD01740 YChEBICHEBI 31252 YChEMBLChEMBL444 YCompTox Dashboard EPA DTXSID5022643ECHA InfoCard100 000 301Chemical and physical dataFormulaC 8H 12N 2O 3Molar mass184 195 g mol 13D model JSmol Interactive imageSMILES O C1NC O NC O C1 CC CCInChI InChI 1S C8H12N2O3 c1 3 8 4 2 5 11 9 7 13 10 6 8 12 h3 4H2 1 2H3 H2 9 10 11 12 13 YKey FTOAOBMCPZCFFF UHFFFAOYSA N Y verify Contents 1 Synthesis 2 Marketing 3 Pharmacology 4 pH buffer 5 Suicide 6 References 7 Further readingSynthesis EditBarbital then called Veronal was first synthesized in 1902 by German chemists Emil Fischer and Joseph von Mering who published their discovery in 1903 1 Barbital was prepared by condensing diethylmalonic ester with urea in the presence of sodium ethoxide or by adding at least two molar equivalents of ethyl iodide to the silver salt of malonylurea barbituric acid or possibly to a basic solution of the acid The result was an odorless slightly bitter white crystalline powder 2 Its introduction followed the investigations of Fischer and von Mering on the pharmacological properties of certain open and closed acylureas then called ureides Led by the impression that hypnotic action appears to be largely dependent on the presence of ethyl groups they prepared diethylacetyl urea diethylmalonyl urea i e Barbital itself and dipropylmalonyl urea All three were found to be hypnotics the first was about equal in power to the already known sulphonal now sulfonmethane whilst the third was four times as powerful but its use was attended by prolonged after effects Veronal was found to be midway 2 Barbital can also be synthesized in a condensation reaction from urea and diethyl 2 2 diethylmalonate a diethyl malonate derivative Marketing Edit Bottle for Veronal crystals named after the Italian city of Verona was the first commercially available barbiturate manufactured by Bayer Barbital was marketed in 1904 by the Bayer company as Veronal A soluble salt of barbital was marketed by the Schering company as Medinal It was dispensed for insomnia induced by nervous excitability 3 unreliable source It was provided in either crystal form or in cachets capsules The therapeutic dose was ten to fifteen grains 0 6 1 grams 3 5 to 4 4 grams 55 to 68 grains is the deadly dose but sleep has also been prolonged up to ten days with recovery Pharmacology EditBarbital 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 Feodorovna confessed to a friend 4 Fatal overdoses of this slow acting hypnotic were not uncommon Pioneering aviator Arthur Whitten Brown of Transatlantic flight of Alcock and Brown fame died of an accidental overdose A photoswitchable derivative of barbital based on a donor acceptor Stenhouse adduct DASA has been developed for research purposes photopharmacology DASA barbital shows neuronal activity via GABAA receptors and reversible photoisomerization in water using cyclodextrin 5 pH buffer EditSolutions of sodium barbital have also been used as pH buffers for biological research e g in immunoelectrophoresis or in fixative solutions 6 7 As barbital is a controlled substance barbital based buffers have largely been replaced by other substances 8 Suicide EditJapanese writer Ryunosuke Akutagawa deliberately overdosed on the drug in 1927 as did Un Chien Andalou actor Pierre Batcheff in 1932 Austrian writer Stefan Zweig in 1942 French Anarchist Germaine Berton in 1942 9 and Greek musician Attik in 1944 During The Holocaust many Jewish residents of Berlin Dresden Wiesbaden and other German cities used Veronal to commit suicide to avoid deportation to concentration camps by the Nazi 10 Regime 11 Alfred Kerr a German theatre critic and essayist suffered a stroke on a trip to Germany after WWII and decided to end his own life via an overdose of Veronal which was procured for him by his wife 12 In the D H Lawrence story The Lovely Lady the titular character dies from a self administered overdose 13 Barbital under the name of Veronal has been used as a plot device in the author Agatha Christie s murder mysteries 14 In Stephen King s The Stand some characters used Veronal in small doses as a way to suppress the ever intensifying nightmares involving the dark man they communally experienced The main character in Dorothy Parker s short story Big Blonde Hazel Morse buys 2 bottles of Veronal tablets over the counter with the intention of committing suicide In Miroslav Krleza s drama Messrs Glembay Irena Danielli Basilides overdosed on Veronal as her third and fatal suicide attempt References Edit Fischer E von Mering J 1903 Ueber eine neue Klasse von Schlafmitteln About a new class of sleeping pills Therapie der Gegenwart in German 44 97 101 a b One or more of the preceding sentences incorporates text from a publication now in the public domain Chisholm Hugh ed 1911 Veronal Encyclopaedia Britannica Vol 27 11th ed Cambridge University Press p 1037 Finley E 1919 Veronal The American Materia Medica Therapeutics and Pharmacognosy p 115 Retrieved 25 July 2015 Dehn L 1922 The Real Tsaritsa Boston Little Brown p 138 Castagna Rossella Maleeva Galyna Pirovano Deborah Matera Carlo Gorostiza Pau 2022 08 17 Donor Acceptor Stenhouse Adduct Displaying Reversible Photoswitching in Water and Neuronal Activity Journal of the American Chemical Society 144 34 15595 15602 doi 10 1021 jacs 2c04920 ISSN 0002 7863 PMID 35976640 S2CID 251623598 Kuhlmann WD 10 September 2006 Buffer Solutions PDF Archived from the original PDF on 9 November 2016 Retrieved 28 July 2014 Ruzin SE 1999 Plant Microtechnique and Microscopy Oxford University Press Archived from the original on 3 June 2019 Retrieved 28 July 2014 Monthony JF Wallace EG Allen DM October 1978 A non barbital buffer for immunoelectrophoresis and zone electrophoresis in agarose gels Clinical Chemistry 24 10 1825 7 doi 10 1093 clinchem 24 10 1825 PMID 568042 Le Matin in French 1942 07 06 retrieved 2022 06 04 I Will Bear Witness by Victor Klemperer Author Martin Chalmers Translator 1998 Cargas Harry J 1999 Problems Unique to the Holocaust Univ Pr of Kentucky p 44 ISBN 9780813121017 Im Interview Judith Kerr Wir waren eine Insel Kultur sueddeutsche de 2008 06 10 Archived from the original on 2008 06 10 Retrieved 2021 07 08 Lawrence D H David Herbert 1988 The virgin and the gypsy and other stories Internet Archive London Marshall Cavendish ISBN 978 0 86307 694 7 A quote from The Murder of Roger Ackroyd www goodreads com Retrieved 2021 10 22 Further reading EditDombrowski SM Krishnan R Witte M Maitra S Diesing C Waters LC Ganguly R October 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 1 69 77 doi 10 1016 s0378 1119 98 00436 3 PMID 9852951 Norena Shopland T he Veronal Mystery Wordcatcher Publishing 2020 Retrieved from https en wikipedia org w index php title Barbital amp oldid 1131485882, wikipedia, wiki, book, books, library,
