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Methyprylon
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Systematic (IUPAC) name |
(RS)-3,3-diethyl-5-methylpiperidine-2,4-dione |
Clinical data |
Trade names |
Dimerin, Methyprylone, Noctan, Noludar |
Legal status |
Schedule III (US) |
Routes |
oral |
Pharmacokinetic data |
Protein binding |
60% |
Half-life |
6-16 hours |
Identifiers |
CAS number |
125-64-4 Y |
ATC code |
N05CE02 |
PubChem |
CID 4162 |
DrugBank |
DB01107 |
ChemSpider |
4018 Y |
UNII |
CUT48I42ON Y |
KEGG |
D01150 N |
ChEMBL |
CHEMBL1200790 N |
Chemical data |
Formula |
C10H17NO2 |
Mol. mass |
183.248 g/mol |
InChI
-
InChI=1S/C10H17NO2/c1-4-10(5-2)8(12)7(3)6-11-9(10)13/h7H,4-6H2,1-3H3,(H,11,13) Y
Key:SIDLZWOQUZRBRU-UHFFFAOYSA-N Y
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N (what is this?) (verify) |
Methyprylon (Noludar) is a sedative of the piperidinedione derivative family developed by Hoffmann-La Roche.[1] This medicine was used for treating insomnia, but is now rarely used as it has been replaced by newer drugs with fewer side effects, such as benzodiazepines.[2] Methyprylon was withdrawn from the US market in June 1989 and the Canadian market in September 1990.
Contents
- 1 Adverse effects
- 2 Pharmacokinetics
- 3 Synthesis
- 4 See also
- 5 References
Adverse effects
Side effects can include skin rash, fever, depression, ulcers or sores in mouth or throat, unusual bleeding or bruising, confusion, fast heartbeat, respiratory depression, swelling of feet or lower legs, dizziness, drowsiness, headache, double vision, clumsiness, constipation, diarrhea, nausea, vomiting, unusual weakness.[citation needed]
Pharmacokinetics
A study of single oral doses of 300 mg in healthy volunteers found that the zero-order absorption model fit the data best. Mean (+/- SD) values for the half-life (9.2 +/- 2.2 h), apparent clearance, (11.91 +/- 4.42 mL/h/kg) and apparent steady-state volume of distribution, (0.97 +/- 0.33 L/kg) were found.[3]
A case report found that the pharmacokinetics of methyprylon were not concentration dependent in an overdose case; explanations included saturation or inhibition of metabolic pathways. The generally accepted half-life for a therapeutic dose was not found appropriate in intoxicated patients and would underestimate the time required to reach a safe concentration of the drug.[4]
Synthesis
Methyprylon may be synthesized starting from an aldol condensation of ethyl 2,2-diethyl-3-oxobutanoate with ethyl formate. The resulting enol is converted to the lactam pyrithyldione by treating with ammonia and heating. The lactam is formylated at position-5 and reduced to yield methyprylon.[5]
See also
- Pyrithyldione
- Piperidione
- Glutethimide
References
- ^ US patent 2680116, Frick, H. & Lutz, A. H., "Piperidiones and Process for the Manufacture thereof", issued 1954-06-01, assigned to Hoffmann-La Roche
- ^ Lomen, P.; Linet, O. I. (1976). "Hypnotic efficacy of triazolam and methyprylon in insomniac in-patients". The Journal of international medical research 4 (1): 55–58. PMID 16792. edit
- ^ Gwilt, P. R.; Pankaskie, M. C.; Thornburg, J. E.; Zustiak, R.; Shoenthal, D. R. (1985). "Pharmacokinetics of methyprylon following a single oral dose". Journal of pharmaceutical sciences 74 (9): 1001–1003. PMID 2866242. edit
- ^ Contos, D. A.; Dixon, K. F.; Guthrie, R. M.; Gerber, N.; Mays, D. C. (1991). "Nonlinear elimination of methyprylon (noludar) in an overdosed patient: Correlation of clinical effects with plasma concentration". Journal of pharmaceutical sciences 80 (8): 768–771. PMID 1686463. edit
- ^ Schnider, O.; Frick, H.; Lutz, A. H. (1954). "Synthesis of new hypnotics from pyridine and piperidine groups". Experientia 10 (3): 135–137. PMID 13161893. edit
Hypnotics/sedatives (N05C)
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GABAA
agonists/PAMs |
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GABAB
agonists |
- 1,4-Butanediol
- Aceburic acid
- GABOB
- GHB (Sodium oxybate)
- GBL
- GVL
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H1 inverse
agonists |
Antihistamines: |
- Captodiame
- Cyproheptadine
- Diphenhydramine
- Doxylamine
- Hydroxyzine
- Methapyrilene
- Pheniramine
- Promethazine
- Propiomazine
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Antidepressants |
- Tricyclic antidepressants
- Amitriptyline
- Doxepin
- Trimipramine, etc.
- Tetracyclic antidepressants
- Mianserin
- Mirtazapine, etc.
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Antipsychotics |
- Typical antipsychotics
- Chlorpromazine
- Thioridazine, etc.
- Atypical antipsychotics
- Olanzapine
- Quetiapine
- Risperidone, etc.
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|
|
α1-Adrenergic
antagonists |
Antidepressants |
- Serotonin antagonists and reuptake inhibitors
- Tricyclic antidepressants
- Amitriptyline
- Doxepin
- Trimipramine, etc.
- Tetracyclic antidepressants
|
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Antipsychotics |
- Typical antipsychotics
- Chlorpromazine
- Thioridazine, etc.
- Atypical antipsychotics
- Olanzapine
- Quetiapine
- Risperidone, etc.
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Others: |
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α2-Adrenergic
agonists |
- 4-NEMD
- Clonidine
- Detomidine
- Dexmedetomidine
- Lofexidine
- Medetomidine
- Romifidine
- Tizanidine
- Xylazine
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5-HT2A
antagonists |
Antidepressants |
- Serotonin antagonists and reuptake inhibitors
- Tricyclic antidepressants
- Amitriptyline
- Doxepin
- Trimipramine, etc.
- Tetracyclic antidepressants
- Mianserin
- Mirtazapine, etc.
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Antipsychotics |
- Typical antipsychotics
- Chlorpromazine
- Thioridazine, etc.
- Atypical antipsychotics
- Olanzapine
- Quetiapine
- Risperidone, etc.
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Others: |
- Eplivanserin
- Niaprazine
- Pruvanserin
- Volinanserin
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Melatonin
agonists |
- Agomelatine
- LY-156,735
- Melatonin
- Ramelteon
- Tasimelteon
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Orexin
antagonists |
- Almorexant
- SB-334,867
- SB-408,124
- SB-649,868
- Suvorexant
- TCS-OX2-29
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Others |
- Acecarbromal
- Apronal
- Bromisoval
- Cannabidiol
- Carbromal
- Embutramide
- Evoxine
- Fenadiazole
- Gabapentin
- Kavalactones
- Mephenoxalone
- Opioids
- Passion flower
- Scopolamine
- UMB68
- Valnoctamide
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English Journal
- Classical genetic analyses of responses to sedative-hypnotic drugs in crosses derived from long-sleep and short-sleep mice.
- de Fiebre CM, Marley RJ, Miner LL, de Fiebre NE, Wehner JM, Collins AC.SourceInstitute for Behavioral Genetics, University of Colorado, Boulder 80309-0447.
- Alcoholism, clinical and experimental research.Alcohol Clin Exp Res.1992 Jun;16(3):511-21.
- A classical (Mendelian) genetic analysis of responses to eight sedative-hypnotic compounds (ethanol, urethane, trifluoroethanol, chloral hydrate, barbital, paraldehyde, methyprylon, pentobarbital) was conducted in crosses derived from mouse lines that were selectively bred for differential duration
- PMID 1352660
- Consequences of the 1989 New York State triplicate benzodiazepine prescription regulations.
- Weintraub M, Singh S, Byrne L, Maharaj K, Guttmacher L.SourceDepartment of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, NY 14642.
- JAMA : the journal of the American Medical Association.JAMA.1991 Nov 6;266(17):2392-7.
- OBJECTIVE: Comparison of psychoactive medication prescribing and Medicaid expenditures before (1987 through 1988) and after (1989 through 1990) institution of the New York State triplicate benzodiazepine regulations.DATA SOURCES: The National Prescription Audit (IMS America, Plymouth Meeting, Pa), N
- PMID 1681121
- Nonlinear elimination of methyprylon (noludar) in an overdosed patient: correlation of clinical effects with plasma concentration.
- Contos DA, Dixon KF, Guthrie RM, Gerber N, Mays DC.SourceDepartment of Pharmacology, College of Medicine, Ohio State University, Columbus 43210.
- Journal of pharmaceutical sciences.J Pharm Sci.1991 Aug;80(8):768-71.
- This is a report of the pharmacokinetics of methyprylon and its major plasma metabolite, 5-methylpyrithyldione, in an overdosed patient using a reversed-phase HPLC assay. The decline in the concentration of plasma methyprylon was nonlinear between 66 and 30 micrograms/mL and linear at concentrations
- PMID 1686463
Japanese Journal
- 腐爛死体からの2,4-Dioxo-3,3-diethyl-5-methylpiperidine(Methyprylon)の検出
- 4081 Doping効果に関する基礎的研究 : Pentobarbital 並びにMethyprylon のマウス自発運動に及ぼす影響について
- 4081 Doping効果に関する基礎的研究 : Pentobarbital 並びにMethyprylon のマウス自発運動に及ぼす影響について
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