Methyprylon

Methyprylon
Clinical data
Trade namesNoludar, Dimerin, Noctan, Methyprylone
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding60%
Elimination half-life6–16 hours
Identifiers
  • (RS)-3,3-diethyl-5-methylpiperidine-2,4-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.004.315 Edit this at Wikidata
Chemical and physical data
FormulaC10H17NO2
Molar mass183.251 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • CCC1(CC)C(=O)NCC(C)C1=O
  • 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)
  • Key:SIDLZWOQUZRBRU-UHFFFAOYSA-N
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Methyprylon, ormethyprylone is a piperidinedione derivative and CNS depressant drug marketed by Hoffmann-La Roche in the 1950s, marketed under the trade name Noludar and advertised as treatment of insomnia as a nonbarbiturate. According to the Encyclopedia of Toxicology (2005), methyprylon was withdrawn from the United States market in 1988.

Pharmacokinetics

A study of single oral doses of 300 mg in healthy volunteers found that a zero-order absorption model best fit the pharmacokinetic data. Mean (+/- SD) values for the elimination half-life (9.2 +/- 2.2 hours), apparent clearance (11.91 +/- 4.42 mL/h/kg), and apparent steady-state volume of distribution (0.97 +/- 0.33 L/kg) were reported.

A case report examining methyprylon overdose found that elimination kinetics were not concentration dependent. The authors suggested that saturation or inhibition of metabolic pathways could explain the observed nonlinear elimination. The therapeutic-dose half-life was considered inappropriate for intoxicated patients and could underestimate the time required to reach safe plasma concentrations.

History

Research & development

Methyprylon was developed by Hoffmann-La Roche in the early 1950s, culminating research beginning in the 1940s as part of a search for nonbarbiturate sedative-hypnotics. Patented in the United States in 1954,

Approval

It was introduced in clinical practice in 1955, marketed under several trade names Roche marketed it as Noludar in North America and the United Kingdom, Noctan in France and Francophone, and as Dimerin in parts of Central Europe. Following the emergence of newer central nervous system depressants with superior therapeutic profiles, these regional variants were progressively phased out, culminating in its final commercial withdrawal from the Canadian market in September 1990.

Clinical use

Early clinical reports described methyprylon as a nonbarbiturate soporific that reliably promoted sleep, and a comparatively mild alternative to barbiturate hypnotics, which were then widely used in clinical practice. Methyprylon launched in Turkey in the year 1960, as seen in a trade advertisement contemporaneous to the year and region.[better source needed]

Following its introduction, methyprylon was evaluated in a variety of clinical settings involving insomnia associated with underlying medical conditions. A 1962 study examined its use in chronic insomniac patients with various physical disorders and reported improvements in sleep among patients with conditions including gastrointestinal disorders, cardiovascular disease, pulmonary disease, diabetes mellitus, epilepsy, alcoholism, cirrhosis, and other chronic illnesses.

Adverse effects

Despite early reports describing methyprylon as an effective hypnotic, concerns regarding intoxication and dependence became increasingly apparent during the following decade. Reports of overdose, suicide attempts, and dependence contributed to a changing assessment of its safety profile. Reports of serious intoxication began appearing in the medical literature as early as 1956. That year, the New England Journal of Medicine published a report describing the first fatal poisoning associated with methyprylon. During the following decade, additional reports documented overdose, suicide attempts, and dependence associated with methyprylon use.

Decline and discontinuation

By the 1970s, methyprylon had largely been replaced by benzodiazepines and their derivatives. A 1976 clinical comparison of methyprylon with triazolam described methyprylon as rarely used and noted that newer drugs, including benzodiazepines, had become preferred alternatives because of their clinical advantages and fewer adverse effects. According to the Encyclopedia of Toxicology (2005), the substance was withdrawn from the United States market in 1988.

References

  1. 1 2 US granted 2680116, Frick H, Lutz AH, "Piperidiones and Process for the Manufacture thereof", published 1954-06-01, issued 1954-06-01, assigned to Hoffmann-La Roche
  2. 1 2 "Encyclopedia of Toxicology". ScienceDirect. Archived from the original on 2024-11-07. Retrieved 2026-07-09.
  3. ↑ Gwilt PR, Pankaskie MC, Thornburg JE, Zustiak R, Shoenthal DR (September 1985). "Pharmacokinetics of methyprylon following a single oral dose". Journal of Pharmaceutical Sciences. 74 (9): 1001–1003. Bibcode:1985JPhmS..74.1001G. doi:10.1002/jps.2600740920. PMID 2866242.
  4. ↑ Contos DA, Dixon KF, Guthrie RM, Gerber N, Mays DC (August 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. Bibcode:1991JPhmS..80..768C. doi:10.1002/jps.2600800813. PMID 1686463.
  5. ↑ NIST Office of Data and Informatics. "Methyprylon". webbook.nist.gov. National Institute of Standards and Technology. Retrieved 2026-07-09.
  6. ↑ Cass LJ, Frederik WS, Andosca JB (October 1955). "Methyprylon, a new sedative and hypnotic drug". The New England Journal of Medicine. 253 (14): 586–591. doi:10.1056/NEJM195510062531402. PMID 13266000.
  7. 1 2 "Methyprylon: Uses, Interactions, Mechanism of Action". DrugBank Online. DrugBank. Retrieved July 9, 2026.{{cite web}}: CS1 maint: url-status (link)
  8. ↑ Stewart JS (December 1956). "Clinical trial of methyprylone, a piperidine hypnotic". British Medical Journal. 2 (5007): 1465–1467. doi:10.1136/bmj.2.5007.1465. PMC 2035974. PMID 13374358.
  9. ↑ Billow BW, Whiteman N, Carey R, Cabodevilla A, Barnes L, Rothman N, et al. (March 1962). "Evaluation of methyprylon in chronic insomniac patients with various physical disorders". Journal of the National Medical Association. 54 (2): 248–250. PMC 2642387. PMID 13869209.
  10. 1 2 Stauss HK (December 1965). "Attempted suicide with methyprylon". JAMA. 194 (10): 1139–1140. doi:10.1001/jama.1965.03090230107037. PMID 5897795.
  11. ↑ Reidt WU (August 1956). "Fatal poisoning with methyprylon (Noludar), a nonbarbiturate sedative". The New England Journal of Medicine. 255 (5): 231–232. doi:10.1056/NEJM195608022550507. PMID 13348845.
  12. ↑ Lomen P, Linet OI (1976). "Hypnotic efficacy of triazolam and methyprylon in insomniac in-patients". The Journal of International Medical Research. 4 (1): 55–58. doi:10.1177/030006057600400108. PMID 16792. S2CID 12500779.

Link: finding far lower toxicity than glutethimide

See also