Doriden

Glutethimide
Systematic (IUPAC) name
	3-ethyl-3-phenyl-piperidine-2,6-dione
Clinical data
Pregnancy; category	C: (United States);
Routes of; administration	oral
Legal status
Legal status	AU: S4 (Prescription only); CA: Schedule IV; DE: Anlage II (Prohibited); US: Schedule II; UN: Psychotropic Schedule III;
Pharmacokinetic data
Bioavailability	Variable (Tmax = 1–6 hours)
Protein binding	~50%
Metabolism	Extensive hepatic
Biological half-life	8–12 hours
Excretion	Renal
Identifiers
CAS Number	77-21-4
ATC code	N05CE01 (WHO)
PubChem	CID 3487
IUPHAR/BPS	7192
DrugBank	DB01437
ChemSpider	3367
UNII	C8I4BVN78E
KEGG	D00532
ChEMBL	CHEMBL1102
Chemical data
Formula	C13H15NO2
Molar mass	217.264 g/mol
	SMILES O=C1NC(CCC1(CC)C2=CC=CC=C2)=O ;
	InChI InChI=1S/C13H15NO2/c1-2-13(10-6-4-3-5-7-10)9-8-11(15)14-12(13)16/h3-7H,2,8-9H2,1H3,(H,14,15,16) ; Key:JMBQKKAJIKAWKF-UHFFFAOYSA-N ;
Physical data
Melting point	84 °C (183 °F)
Solubility in water	999 mg/L (30 °C/86 °F) mg/mL (20 °C)
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/30 08:47:19」(JST)

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Glutethimide is a hypnotic sedative that was introduced by Ciba^[2] in 1954 as a safe alternative to barbiturates to treat insomnia. Before long, however, it had become clear that glutethimide was just as likely to cause addiction and caused similarly severe withdrawal symptoms. Doriden was the brand-name version of the drug; it was also available under the brand names Elrodorm, Noxyron, Glimid and others. Both the generic and brand-name forms are very rarely prescribed today. Current production levels in the United States (the annual quota for manufacturing imposed by the DEA has been three grams, enough for six Doriden tablets, for a number of years) point to it only being used in small scale research.

Long term use

Long term use rebound effects, which resembled those seen in withdrawal, have anecdotally been described in patients who were still taking a stable dose of the drug. The symptoms included delirium, hallucinosis, convulsions and fever.^[3]

Recreational use

Glutethimide is a CYP2D6 enzyme inducer. When taken with codeine,"hits", "cibas and codeine ", it enables the body to convert higher amounts of the codeine (higher than the average 5 - 10%) to morphine. The general sedative effect also adds to the effect of the combination. It produces an intense euphoria similar to IV heroin use. The effect was also used clinically, including some research in the 1970s in various countries of using it under carefully monitored circumstances as a form of oral opioid agonist substitution therapy, e.g. as a Substitutionmittel that may be a useful alternative to methadone.^[4]^[5] The demand for this combination in Philadelphia, Pittsburgh, Newark, NYC, Boston, Baltimore, and surrounding areas of other states and perhaps elsewhere, has led to small-scale clandestine synthesis of glutethimide since 1984,^[6] a process that is, like methaqualone (Quaalude) synthesis, somewhat difficult and fraught with potential bad outcomes when less-than-gifted chemists are doing the deed with industrial-grade precursors without adequate quality control. The fact that the simpler clandestine synthesis of other extinct pharmaceutical depressants like ethchlorvynol, methyprylon, or the oldest barbiturates is not reported would seem to point to a high level of motivation surrounding a unique drug, again much like methaqualone. Doriden was discontinued in the US by manufacturers in 1993. Analysis of confiscated glutethimide seems to invariably show the drug or the results of attempted synthesis, whereas purported methaqualone is in a significant minority of cases found to be inert, or contain diphenhydramine or benzodiazepines.^[7]

Legal status

Glutethimide is a Schedule II drug under the Convention on Psychotropic Substances.^[8] It was originally a Schedule III drug in the United States under the Controlled Substances Act, but in 1991 it was upgraded to Schedule II,^[9] after it was discovered that misuse combined with codeine increased the effect of the codeine and deaths had resulted from the combination.^[10]^[11] It has a DEA ACSCN of 2550 and a 2013 production quota of 3 g.

Chemistry

Glutethimide (2-ethyl-2-phenylgutarimide) is synthesized by addition of 2-phenylbutyronitrile to the methylacrylate (Michael reaction), and the subsequent alkaline hydrolysis of the nitrile group in the obtained compound into an amide group, and the subsequent acidic cyclization of the product into the desired glutethimide.^[12] The (R) isomer has a faster onset and more potent anticonvulsant activity in animal models than the (S) isomer.^[13]

References

^ Barceloux, Donald G. (2012). Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Hoboken, N.J.: John Wiley & Sons, Inc. pp. 492–493. ISBN 978-0-471-72760-6.
^ US patent 2673205, Hoffmann, K.; Tagmann, E., "3-Disubstituted Dioxopiperidines and the Manufacture thereof", issued 1954-03-23, assigned to Ciba
^ Cookson, J. C. (1995). "Rebound exacerbation of anxiety during prolonged tranquilizer ingestion". Journal of the Royal Society of Medicine 88 (9): 544. PMC 1295346. PMID 7562864.
^ Popa, D.; Loghin, F.; Imre, S.; Curea, E. (2003). "The Study of Codeine-Gluthetimide Pharmacokinetic Interaction in Rats". Journal of Pharmaceutical and Biomedical Analysis 32 (4–5): 867–877. doi:10.1016/s0731-7085(03)00189-4. PMID 12899973.
^ Khajawall, A. M.; Sramek, J. J. Jr.; Simpson, G. M. (1982). "'Loads' Alert". The Western Journal of Medicine 137 (2): 166–168. PMC 1274052. PMID 7135952.
^ Gahlinger, 2001, pp 203
^ Gahlinger, 2001 Ch "Methaqualone & Glutethimide"
^ "List of psychotropic substances under international control" (pdf). INCB.
^ "Code of Federal Regulations Section 1308.12 Schedule II". DEA.
^ Havier, R. G.; Lin, R. (1985). "Deaths as a Result of a Combination of Codeine and Glutethimide". Journal of Forensic Sciences 30 (2): 563–566. PMID 3998703.
^ Feuer, E.; French, J. (1984). "Descriptive Epidemiology of Mortality in New Jersey due to Combinations of Codeine and Glutethimide". American Journal of Epidemiology 119 (2): 202–207. PMID 6695899.
^ Tagmann, E.; Sury, E.; Hoffmann, K. (1952). "Über Alkylenimin-Derivate. 2. Mitteilung". Helvetica Chimica Acta 35 (5): 1541–1548. doi:10.1002/hlca.19520350516.
DE patent 950193, Hoffmann, K. & Tagmann, E., "Verfahren zur Herstellung neuer Dioxopiperidine"
US patent 2673205, Hoffmann, K. & Tagmann, E., "3-disubstituted dioxopiperidines and the manufacture thereof"
Salmon-Legagneur, F.; Neveu, C. (1952). Compt. Rend. 234: 1060. Missing or empty |title= (help)
Salmon-Legagneur, F.; Neveu, C. (1953). Bull. Soc. Chim. France 70. Missing or empty |title= (help)
^ Annual Report in Medicinal Chemistry Volume 12 page 13

English Journal

A study of the risk of mental retardation among children of pregnant women who have attempted suicide by means of a drug overdose.

Petik D, Czeizel B, Banhidy F, Czeizel AE.SourceFoundation for the Community Control of Hereditary Diseases, Budapest, Hungary.
Journal of injury & violence research.J Inj Violence Res.2012 Jan;4(1):10-9. Epub 2011 Apr 16.
BACKGROUND: The aim of the study was to estimate the effect on the fetal development of high doses of prescription drugs taken as a suicide attempt during pregnancy.METHODS: Pregnant women were identified among self-poisoned females in the toxicological inpatient clinic in Budapest between 1960 and
PMID 21502792

Japanese Journal

分娩第1期に使用せるDoridenの効果

産婦人科の世界 14(3), ????, 1962-03
NAID 40017836810

INDUCTION OF HEPATIC CARISOPRODOL-METABOLIZING ENZYME BY PRETREATMENT WITH SOME NEUROPSYCHOTROPIC DRUGS IN RATS

The Japanese Journal of Pharmacology 11(1), 31-36, 1961
NAID 130001942765

術前処理としてのDoriden投与の効果について

産科と婦人科 26(9), ????, 1959-09
NAID 40017817901

Related Pictures

DORIDEN CIBA Plåtask på Tradera.com - Medicinska prylar - Samlarsaker | Mark My Place Blog - MarkMyPlace! Tetronal - WikiVisually Addictive prescription medicine bottles (Doriden, Hydrocodone Stock Photo, Royalty 500 Mg Stock Photos & 500 Mg Stock Images - Alamy Deco Dog's Ephemera - BARBITURATE Glutéthimide ; doriden

[1] Barceloux, Donald G. (2012). Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Hoboken, N.J.: John Wiley & Sons, Inc. pp. 492–493. ISBN 978-0-471-72760-6.

[2] US patent 2673205, Hoffmann, K.; Tagmann, E., "3-Disubstituted Dioxopiperidines and the Manufacture thereof", issued 1954-03-23, assigned to Ciba

[3] Cookson, J. C. (1995). "Rebound exacerbation of anxiety during prolonged tranquilizer ingestion". Journal of the Royal Society of Medicine 88 (9): 544. PMC 1295346. PMID 7562864.

[4] Popa, D.; Loghin, F.; Imre, S.; Curea, E. (2003). "The Study of Codeine-Gluthetimide Pharmacokinetic Interaction in Rats". Journal of Pharmaceutical and Biomedical Analysis 32 (4–5): 867–877. doi:10.1016/s0731-7085(03)00189-4. PMID 12899973.

[5] Khajawall, A. M.; Sramek, J. J. Jr.; Simpson, G. M. (1982). "'Loads' Alert". The Western Journal of Medicine 137 (2): 166–168. PMC 1274052. PMID 7135952.

[6] Gahlinger, 2001, pp 203

[7] Gahlinger, 2001 Ch "Methaqualone & Glutethimide"

[8] "List of psychotropic substances under international control" (pdf). INCB.

[9] "Code of Federal Regulations Section 1308.12 Schedule II". DEA.

[10] Havier, R. G.; Lin, R. (1985). "Deaths as a Result of a Combination of Codeine and Glutethimide". Journal of Forensic Sciences 30 (2): 563–566. PMID 3998703.

[11] Feuer, E.; French, J. (1984). "Descriptive Epidemiology of Mortality in New Jersey due to Combinations of Codeine and Glutethimide". American Journal of Epidemiology 119 (2): 202–207. PMID 6695899.

[12] Tagmann, E.; Sury, E.; Hoffmann, K. (1952). "Über Alkylenimin-Derivate. 2. Mitteilung". Helvetica Chimica Acta 35 (5): 1541–1548. doi:10.1002/hlca.19520350516.
DE patent 950193, Hoffmann, K. & Tagmann, E., "Verfahren zur Herstellung neuer Dioxopiperidine"
US patent 2673205, Hoffmann, K. & Tagmann, E., "3-disubstituted dioxopiperidines and the manufacture thereof"
Salmon-Legagneur, F.; Neveu, C. (1952). Compt. Rend. 234: 1060. Missing or empty |title= (help)
Salmon-Legagneur, F.; Neveu, C. (1953). Bull. Soc. Chim. France 70. Missing or empty |title= (help)

[13] Annual Report in Medicinal Chemistry Volume 12 page 13

v t e GABA_A receptor positive allosteric modulators

Alcohols	Brometone Butanol Chloralodol Chlorobutanol (cloretone) Ethanol (drinking alcohol) Ethchlorvynol Isobutanol Isopropanol Menthol Methanol Methylpentynol Pentanol Petrichloral Propanol tert-Butanol (2M2P) tert-Pentanol (2M2B) Tribromoethanol Trichloroethanol Triclofos Trifluoroethanol

Barbiturates	(-)-DMBB Allobarbital Alphenal Amobarbital Aprobarbital Barbexaclone Barbital Benzobarbital Benzylbutylbarbiturate Brallobarbital Brophebarbital Butabarbital/Secbutabarbital Butalbital Buthalital Butobarbital Butallylonal Carbubarb CP-1414S Crotylbarbital Cyclobarbital Cyclopentobarbital Difebarbamate Enallylpropymal Ethallobarbital Eterobarb Febarbamate Heptabarb Heptobarbital Hexethal Hexobarbital Metharbital Methitural Methohexital Methylphenobarbital Narcobarbital Nealbarbital Pentobarbital Phenallymal Phenobarbital Phetharbital Primidone Probarbital Propallylonal Propylbarbital Proxibarbital Reposal Secobarbital Sigmodal Spirobarbital Talbutal Tetrabamate Tetrabarbital Thialbarbital Thiamylal Thiobarbital Thiobutabarbital Thiopental Thiotetrabarbital Valofane Vinbarbital Vinylbital

Benzodiazepines	2-Oxoquazepam 3-Hydroxyphenazepam Adinazolam Alprazolam Arfendazam Avizafone Bentazepam Bretazenil Bromazepam Brotizolam Camazepam Carburazepam Chlordiazepoxide Ciclotizolam Cinazepam Cinolazepam Clazolam Climazolam Clobazam Clonazepam Clonazolam Clorazepate Clotiazepam Cloxazolam Cyprazepam Delorazepam Demoxepam Diazepam Diclazepam Doxefazepam Elfazepam Estazolam Ethyl carfluzepate Ethyl dirazepate Ethyl loflazepate Etizolam EVT-201 FG-8205 Fletazepam Flubromazepam Flubromazolam Fludiazepam Flunitrazepam Flurazepam Flutazolam Flutemazepam Flutoprazepam Fosazepam Gidazepam Halazepam Haloxazolam Iclazepam Imidazenil Irazepine Ketazolam Lofendazam Lopirazepam Loprazolam Lorazepam Lormetazepam Meclonazepam Medazepam Menitrazepam Metaclazepam Mexazolam Midazolam Motrazepam N-Desalkylflurazepam Nifoxipam Nimetazepam Nitrazepam Nitrazepate Nitrazolam Nordazepam Nortetrazepam Oxazepam Oxazolam Phenazepam Pinazepam Pivoxazepam Prazepam Premazepam Proflazepam Pyrazolam QH-II-66 Quazepam Reclazepam Remimazolam Rilmazafone Ripazepam Ro48-6791 Ro48-8684 SH-053-R-CH3-2′F Sulazepam Temazepam Tetrazepam Tolufazepam Triazolam Triflubazam Triflunordazepam (Ro5-2904) Tuclazepam Uldazepam Zapizolam Zolazepam Zomebazam

Carbamates	Carisbamate Carisoprodol Clocental Cyclarbamate Difebarbamate Emylcamate Ethinamate Febarbamate Felbamate Hexapropymate Lorbamate Mebutamate Meprobamate Nisobamate Pentabamate Phenprobamate Procymate Styramate Tetrabamate Tybamate

Flavonoids	6-Methylapigenin Ampelopsin (dihydromyricetin) Apigenin Baicalein Baicalin Catechin EGC EGCG Hispidulin Linarin Luteolin Rc-OMe Skullcap constituents (e.g., baicalin) Wogonin

Imidazoles	Etomidate Metomidate Propoxate

Kava constituents	10-Methoxyyangonin 11-Methoxyyangonin 11-Hydroxyyangonin Desmethoxyyangonin 11-Methoxy-12-hydroxydehydrokavain 7,8-Dihydroyangonin Kavain 5-Hydroxykavain 5,6-Dihydroyangonin 7,8-Dihydrokavain 5,6,7,8-Tetrahydroyangonin 5,6-Dehydromethysticin Methysticin 7,8-Dihydromethysticin Yangonin

Monoureides	Acecarbromal Apronal (apronalide) Bromisoval Carbromal Capuride Ectylurea

Neuroactive steroids	Acebrochol Allopregnanolone (SAGE-547) Alfadolone Alfaxalone Anabolic steroids 3α-Androstanediol Androstenol Androsterone Cholesterol DHDOC 3α-DHP 5α-DHP 5β-DHP DHT Etiocholanolone Ganaxolone Hydroxydione Minaxolone Org 20599 Org 21465 Pregnanolone (eltanolone) Progesterone Quingestrone Renanolone SAGE-105 SAGE-217 SAGE-324 SAGE-516 SAGE-689 SAGE-872 Testosterone THDOC

Nonbenzodiazepines	β-Carbolines: Abecarnil Gedocarnil Harmane SL-651,498 ZK-93423; Cyclopyrrolones: Eszopiclone Pagoclone Pazinaclone Suproclone Suriclone Zopiclone; Imidazopyridines: Alpidem DS-1 Necopidem Saripidem Zolpidem; Pyrazolopyrimidines: Divaplon Fasiplon Indiplon Lorediplon Ocinaplon Panadiplon Taniplon Zaleplon; Others: Adipiplon CGS-8216 CGS-9896 CGS-13767 CGS-20625 CL-218,872 CP-615,003 CTP-354 ELB-139 GBLD-345 JM-1232 L-838,417 Lirequinil (Ro41-3696) NS-2664 NS-2710 NS-11394 Pipequaline ROD-188 RWJ-51204 SB-205,384 SX-3228 TGSC01AA TP-003 TPA-023 TP-13 U-89843A U-90042 Viqualine Y-23684

Phenols	Fospropofol Propofol Thymol

Piperidinediones	Glutethimide Methyprylon Piperidione Pyrithyldione

Pyrazolopyridines	Cartazolate Etazolate ICI-190,622 Tracazolate

Quinazolinones	Afloqualone Cloroqualone Diproqualone Etaqualone Mebroqualone Mecloqualone Methaqualone Methylmethaqualone Nitromethaqualone SL-164

Volatiles/gases	Acetone Acetophenone Acetylglycinamide chloral hydrate Aliflurane Benzene Butane Butylene Centalun Chloral Chloral betaine Chloral hydrate Chloroform Cryofluorane Desflurane Dichloralphenazone Dichloromethane Diethyl ether Enflurane Ethyl chloride Ethylene Fluroxene Gasoline Halopropane Halothane Isoflurane Kerosine Methoxyflurane Methoxypropane Nitric oxide Nitrogen Nitrous oxide Norflurane Paraldehyde Propane Propylene Roflurane Sevoflurane Synthane Teflurane Toluene Trichloroethane (methyl chloroform) Trichloroethylene Vinyl ether

Others/unsorted	3-Hydroxybutanal α-EMTBL AA-29504 Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium bromide, sodium bromide) Carbamazepine Chloralose Chlormezanone Clomethiazole DEABL Dihydroergolines (e.g., dihydroergocryptine, dihydroergosine, dihydroergotamine, ergoloid (dihydroergotoxine)) DS2 Efavirenz Etazepine Etifoxine Fenamates (e.g., flufenamic acid, mefenamic acid, niflumic acid, tolfenamic acid) Fluoxetine Flupirtine Hopantenic acid Lanthanum Lavender oil Lignans (e.g., 4-O-methylhonokiol, honokiol, magnolol, obovatol) Loreclezole Menthyl isovalerate (validolum) Monastrol Niacin Nicotinamide (niacinamide) Org 25,435 Phenytoin Propanidid Retigabine (ezogabine) Safranal Seproxetine Stiripentol Sulfonylalkanes (e.g., sulfonmethane (sulfonal), tetronal, trional) Terpenoids (e.g., borneol) Topiramate Valerian constituents (e.g., isovaleric acid, isovaleramide, valerenic acid, valerenol) Unsorted benzodiazepine site PAMs: MRK-409 (MK-0343) TCS-1105 TCS-1205

See also: GABAergics

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