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Identification
NameMethyprylon
Accession NumberDB01107  (APRD00734)
Typesmall molecule
Groupsapproved, illicit, withdrawn
Description

Methyprylon is a sedative of the piperidinedione derivative family. This medicine was used for treating insomnia, but is now rarely used as it has been replaced by newer drugs with less side effects, such as benzodiazepines. Methyprylon was withdrawn from the US market in June 1965 and the Canadian market in September 1990. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
MethprylonNot AvailableNot Available
MethyprolonNot AvailableNot Available
MethyprylonNot AvailableINN
MethypryloneFrenchINN
MethyprylonumLatinINN
MetiprilonNot AvailableNot Available
MetiprilonaSpanishINN
MetipriloneNot AvailableNot Available
NoludarNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
DimerinNot Available
NoctanNot Available
NodularNot Available
NoludarNot Available
Brand mixturesNot Available
Categories
CAS number125-64-4
WeightAverage: 183.2475
Monoisotopic: 183.125928793
Chemical FormulaC10H17NO2
InChI KeySIDLZWOQUZRBRU-UHFFFAOYSA-N
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)
IUPAC Name
3,3-diethyl-5-methylpiperidine-2,4-dione
SMILES
CCC1(CC)C(=O)NCC(C)C1=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPiperidines
SubclassPiperidinones
Direct parentPiperidinediones
Alternative parentsDelta Lactams; Secondary Carboxylic Acid Amides; Ketones; Polyamines; Carboxylic Acids
Substituentsdelta-lactam; secondary carboxylic acid amide; carboxamide group; lactam; ketone; polyamine; carboxylic acid derivative; carboxylic acid; organonitrogen compound; carbonyl group
Classification descriptionThis compound belongs to the piperidinediones. These are compounds containing a piperidine ring which bears two ketones.
Pharmacology
IndicationFor the treatment of insomnia.
PharmacodynamicsMethyprylon, a piperidinedione CNS depressant, is close to barbituric acid in structure, but different enough to be called a "non-barbiturate" sedative-hynotic. Methyprylon is used for insomnia and daytime tension. Methyprylon depresses the activity of muscle tissues, the heart, and the respiratory system.
Mechanism of actionMethyprylon binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding60%
Metabolism

Hepatic. Methyprylon is almost completely metabolized.

Route of eliminationNot Available
Half life6-16 hours
ClearanceNot Available
ToxicitySymptoms of overdose include excitation and convulsions.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9958
Caco-2 permeable + 0.5745
P-glycoprotein substrate Non-substrate 0.6409
P-glycoprotein inhibitor I Inhibitor 0.5252
P-glycoprotein inhibitor II Non-inhibitor 0.8315
Renal organic cation transporter Non-inhibitor 0.8494
CYP450 2C9 substrate Non-substrate 0.8971
CYP450 2D6 substrate Non-substrate 0.8024
CYP450 3A4 substrate Non-substrate 0.5391
CYP450 1A2 substrate Non-inhibitor 0.8306
CYP450 2C9 substrate Non-inhibitor 0.8167
CYP450 2D6 substrate Non-inhibitor 0.9028
CYP450 2C19 substrate Non-inhibitor 0.8604
CYP450 3A4 substrate Non-inhibitor 0.8925
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.922
Ames test Non AMES toxic 0.7267
Carcinogenicity Non-carcinogens 0.8355
Biodegradation Not ready biodegradable 0.866
Rat acute toxicity 2.3600 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9762
hERG inhibition (predictor II) Non-inhibitor 0.9295
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility1.15E+004 mg/LNot Available
logP0.78SANGSTER (1994)
Predicted Properties
PropertyValueSource
water solubility1.13e+01 g/lALOGPS
logP0.94ALOGPS
logP1.88ChemAxon
logS-1.2ALOGPS
pKa (strongest acidic)14.53ChemAxon
pKa (strongest basic)-3.1ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area46.17ChemAxon
rotatable bond count2ChemAxon
refractivity50.25ChemAxon
polarizability19.95ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Contos DA, Dixon KF, Guthrie RM, Gerber N, Mays DC: Nonlinear elimination of methyprylon (noludar) in an overdosed patient: correlation of clinical effects with plasma concentration. J Pharm Sci. 1991 Aug;80(8):768-71. Pubmed
  2. Gwilt PR, Pankaskie MC, Thornburg JE, Zustiak R, Shoenthal DR: Pharmacokinetics of methyprylon following a single oral dose. J Pharm Sci. 1985 Sep;74(9):1001-3. Pubmed
  3. Lomen P, Linet OI: Hypnotic efficacy of triazolam and methyprylon ininsomniac in-patients. J Int Med Res. 1976;4(1):55-8. Pubmed
External Links
ResourceLink
KEGG DrugD01150
PubChem Compound4162
PubChem Substance46506891
ChemSpider4018
Therapeutic Targets DatabaseDAP000683
PharmGKBPA164746748
WikipediaMethyprylon
ATC CodesN05CE02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Gamma-aminobutyric acid receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. de Fiebre CM, Marley RJ, Miner LL, de Fiebre NE, Wehner JM, Collins AC: Classical genetic analyses of responses to sedative-hypnotic drugs in crosses derived from long-sleep and short-sleep mice. Alcohol Clin Exp Res. 1992 Jun;16(3):511-21. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. GABA-A receptor (anion channel)

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: positive allosteric modulator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details
Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

References:

  1. ChEMBL Compound Report Card (Accessed December 2013)

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13