Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/28 11:07:08」(JST)

wiki en

Bemegride (also marketed as Megimide) is a central nervous system stimulant and antidote for barbiturate poisoning^[1] as its chemoreceptor agonism increases mean tidal volume, thereby increasing respiration and the concentration of O₂ in blood although it may be theoretically used as a supportive measure in treating any depressant overdose. The drug's synthesis was invented in 1911.^[2]

As with other chemoreceptor agonists, it is a potent emetic at doses above those normally used in management of barbiturate overdose although emesis and aspiration are a concern during treatment.

John Bodkin Adams case

Bemegride is notable in legal history as the drug suspected serial killer Dr John Bodkin Adams failed to prescribe correctly to his patient Gertrude Hullett. Hullett took an overdose of barbiturates on 19 July 1956 but Adams only gave her a single 10cc dose of bemegride three days later on the 22nd, despite having acquired 100cc for her treatment. Hullett died the next day on 23 July 1956. Adams was charged but never tried for her murder.^[3]

Animal use

Bemegride is also used to induce convulsions in experimental animals.^[4]

Synthesis

Bemegride synthesis:^[2]

The original synthesis involves first the condensation of methylethylketone with two equivalents of cyanoacetamide. The product can be rationalized by assuming first aldol condensation of ketone and active methylene compound followed by dehydration to give 3. Conjugate addition of a second molecule of cyanoacetamide would afford 4. Addition of one of the amide amines to the nitrile would then afford the iminonitrile 5. The observed product 6 can be rationalized by assuming loss of the carboxamide under strongly basic conditions. Decarboxylative hydrolysis of 6 then leads to bemigride 7.

References

^ Hofmeister, Alfred (2000). "Analeptics". Ullmann's Encyclopedia of Industrial Chemistry: 1–2. doi:10.1002/14356007.a02_267.
^ ^a ^b Thole, Ferdinand Bernard; Thorpe, Jocelyn Field (1911). "LIII.—The formation and reactions of iminocompounds. Part XV. The production of imino-derivatives of piperidine leading to the formation of the ββ-disubstituted glutaric acids". Journal of the Chemical Society, Transactions 99: 422–448. doi:10.1039/CT9119900422.
^ Cullen, Pamela V., A Stranger in Blood: The Case Files on Dr John Bodkin Adams, London, Elliott & Thompson, 2006, ISBN 1-904027-19-9
^ Definition: bemegride from Online Medical Dictionary

This drug article relating to the respiratory system is a stub. You can help Wikipedia by expanding it.

English Journal

Electroencephalographic features of familial spontaneous epileptic cats.

Hasegawa D1, Mizoguchi S2, Kuwabara T2, Hamamoto Y2, Ogawa F3, Matsuki N3, Uchida K4, Fujita M2.
Epilepsy research.Epilepsy Res.2014 Aug;108(6):1018-25. doi: 10.1016/j.eplepsyres.2014.05.007. Epub 2014 May 14.
A feline strain of familial spontaneous epileptic cats (FSECs) with typical limbic seizures was identified in 2010, and have been maintained as a novel animal model of genetic epilepsy. In this study, we characterized the electroencephalographic (EEG) features of FSECs. On scalp EEG under sedation,
PMID 24893833

Carisoprodol tolerance and precipitated withdrawal.

Gatch MB1, Nguyen JD, Carbonaro T, Forster MJ.
Drug and alcohol dependence.Drug Alcohol Depend.2012 Jun 1;123(1-3):29-34. doi: 10.1016/j.drugalcdep.2011.10.010. Epub 2011 Nov 4.
AIMS: Carisoprodol is a muscle relaxant that acts at the GABA(A) receptor. Concerns about the abuse liability of carisoprodol are increasing, but evidence that carisoprodol produces tolerance and a significant withdrawal syndrome has yet to be established. The purpose of the current study was to det
PMID 22055010

Carisoprodol-mediated modulation of GABAA receptors: in vitro and in vivo studies.

Gonzalez LA1, Gatch MB, Taylor CM, Bell-Horner CL, Forster MJ, Dillon GH.
The Journal of pharmacology and experimental therapeutics.J Pharmacol Exp Ther.2009 May;329(2):827-37. doi: 10.1124/jpet.109.151142. Epub 2009 Feb 24.
Carisoprodol is a frequently prescribed muscle relaxant. In recent years, this drug has been increasingly abused. The effects of carisoprodol have been attributed to its metabolite, meprobamate, a controlled substance that produces sedation via GABA(A) receptors (GABA(A)Rs). Given the structural sim
PMID 19244096

Japanese Journal

False Lateralization of Mesial Temporal Lobe Epilepsy by Noninvasive Neurophysiological Examinations : Case Report

Neurologia medico-chirurgica 46(10), 518-521, 2006-10-15
NAID 110004849270

C-28 カイニン酸局所注入てんかんモデルに対するbemegride投与の影響について

日本てんかん学会プログラム・予稿集 (32), 141, 1998-10-09
NAID 110002671261

脳神経外科領域におけるFunctional MRIの臨床応用について

CI研究 : progress in computed imaging 19(3), 255-260, 1997-09-30
NAID 10009799893

「ベメグリド」

Bemegride
Systematic (IUPAC) name
	4-ethyl-4-methylpiperidine-2,6-dione
Clinical data
Trade names	Mikedimide (Panray), Eukraton (Nordmark), Malysol (Arco, Switzerland), Megimide (Nicholas)
AHFS/Drugs.com	International Drug Names
Legal status	AU: S4 (Prescription only);
Identifiers
CAS Number	64-65-3
ATC code	R07AB05
PubChem	CID 2310
ChemSpider	2220
UNII	57DQA39DO2
KEGG	D01957
ChEMBL	CHEMBL1214192
Synonyms	Methetharimide; β,β-methylethylglutarimide
Chemical data
Formula	C8H13NO2
Molar mass	155.194 g/mol
	SMILES O=C1NC(=O)CC(CC)(C1)C ;
	InChI InChI=1S/C8H13NO2/c1-3-8(2)4-6(10)9-7(11)5-8/h3-5H2,1-2H3,(H,9,10,11) ; Key:ORRZGUBHBVWWOP-UHFFFAOYSA-N ;
Physical data
Melting point	127 °C (261 °F)
(verify)