Methyprylon

Methyprylon

Systematic (IUPAC) name
(RS)-3,3-diethyl-5-methylpiperidine-2,4-dione
Clinical data
Trade names	Dimerin, Methyprylone, Noctan, Noludar
Pregnancy cat.	?
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	APRD00734
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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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 This medicine was used for treating insomnia, but is now rarely used as it has been replaced by newer drugs with fewer side effects, such as benzodiazepines.^[2] Methyprylon was withdrawn from the US market in June 1989 and the Canadian market in September 1990.

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 the pharmacokinetics of methyprylon nonlinear (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 postion-5 and reduced to yield methyprylon.^[5]

See also

• Pyrithyldione
• Piperidione
• Glutethimide

References

1. ^ US patent 2680116, Frick, H. & Lutz, A. H., "Piperidiones and Process for the Manufacture thereof", issued 1954-06-01, assigned to Hoffmann-La Roche 
2. ^ 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
3. ^ 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
4. ^ 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
5. ^ 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