Methyprylon

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Methyprylon
Methyprylon.svg
Methyprylon ball-and-stick.png
Systematic (IUPAC) name
(RS)-3,3-diethyl-5-methylpiperidine-2,4-dione
Clinical data
Trade names Dimerin, Methyprylone, Noctan, Noludar
Legal status
Routes oral
Pharmacokinetic data
Protein binding 60%
Half-life 6-16 hours
Identifiers
CAS number 125-64-4 YesY
ATC code N05CE02
PubChem CID 4162
DrugBank DB01107
ChemSpider 4018 YesY
UNII CUT48I42ON YesY
KEGG D01150 N
ChEMBL CHEMBL1200790 N
Chemical data
Formula C10H17NO2 
Mol. mass 183.248 g/mol
 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developed by Hoffmann-La Roche.[1] This medicine was used for treating insomnia, but is now rarely used as it has been replaced by newer drugs with fewer side effects, such as benzodiazepines.[2] Methyprylon was withdrawn from the US market in June 1989 and the Canadian market in September 1990. Some other trade names are Noctan and Dimerin.

Adverse effects[edit]

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[edit]

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[edit]

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]

Methyprylon synth.tif

See also[edit]

References[edit]

  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. doi:10.1002/jps.2600740920. 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. doi:10.1002/jps.2600800813. 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. doi:10.1007/bf02158518. PMID 13161893.  edit