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Identification
NameMethyprylon
Accession NumberDB01107  (APRD00734)
TypeSmall Molecule
GroupsApproved, Illicit, Withdrawn
DescriptionMethyprylon 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 This medicine was used for treating insomnia, but is now rarely used as it has been replaced by newer drugs with less side effects, such as benzodiazepines. Methyprylon was withdrawn from the US market in June 1965 and the Canadian market in September 1990.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
Methprylon
Methyprolon
Methyprylon
Methyprylone
Methyprylonum
Metiprilon
Metiprilona
Metiprilone
Noludar
External Identifiers
  • Dea No. 2575
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DimerinNot Available
NoctanNot Available
NodularNot Available
NoludarNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIICUT48I42ON
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
Pharmacology
IndicationFor the treatment of insomnia.
Structured Indications Not Available
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Gamma-aminobutyric acid receptor subunit alpha-1Proteinyes
agonist
HumanP14867 details
GABA-A receptor (anion channel)Protein groupyes
positive allosteric modulator
Humannot applicabledetails
Related Articles
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
Interactions
Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Methyprylon can be increased when it is combined with Abiraterone.Approved
AmiodaroneThe metabolism of Methyprylon can be decreased when combined with Amiodarone.Approved, Investigational
ArtemetherThe metabolism of Methyprylon can be decreased when combined with Artemether.Approved
AtomoxetineThe metabolism of Methyprylon can be decreased when combined with Atomoxetine.Approved
BetaxololThe metabolism of Methyprylon can be decreased when combined with Betaxolol.Approved
BupropionThe metabolism of Methyprylon can be decreased when combined with Bupropion.Approved
CelecoxibThe metabolism of Methyprylon can be decreased when combined with Celecoxib.Approved, Investigational
ChloroquineThe metabolism of Methyprylon can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Methyprylon can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Methyprylon can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Methyprylon can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Methyprylon can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Methyprylon can be decreased when combined with Citalopram.Approved
ClemastineThe metabolism of Methyprylon can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Methyprylon can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Methyprylon can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Methyprylon can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Methyprylon can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Methyprylon can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Methyprylon can be decreased when combined with Cocaine.Approved, Illicit
DarifenacinThe metabolism of Methyprylon can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Methyprylon can be increased when it is combined with Darunavir.Approved
DelavirdineThe metabolism of Methyprylon can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Methyprylon can be decreased when combined with Desipramine.Approved
DiphenhydramineThe metabolism of Methyprylon can be decreased when combined with Diphenhydramine.Approved
DronedaroneThe metabolism of Methyprylon can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Methyprylon can be decreased when combined with Duloxetine.Approved
EliglustatThe metabolism of Methyprylon can be decreased when combined with Eliglustat.Approved
FluoxetineThe metabolism of Methyprylon can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Methyprylon can be decreased when combined with Fluvoxamine.Approved, Investigational
HaloperidolThe metabolism of Methyprylon can be decreased when combined with Haloperidol.Approved
ImipramineThe metabolism of Methyprylon can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Methyprylon can be decreased when combined with Indinavir.Approved
IsoniazidThe metabolism of Methyprylon can be decreased when combined with Isoniazid.Approved
KetoconazoleThe metabolism of Methyprylon can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Methyprylon can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Methyprylon can be decreased when combined with Lorcaserin.Approved
LumefantrineThe metabolism of Methyprylon can be decreased when combined with Lumefantrine.Approved
MethadoneThe metabolism of Methyprylon can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Methyprylon can be decreased when combined with Methotrimeprazine.Approved
MetoprololThe metabolism of Methyprylon can be decreased when combined with Metoprolol.Approved, Investigational
MirabegronThe metabolism of Methyprylon can be decreased when combined with Mirabegron.Approved
NevirapineThe metabolism of Methyprylon can be decreased when combined with Nevirapine.Approved
NicardipineThe metabolism of Methyprylon can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Methyprylon can be decreased when combined with Nilotinib.Approved, Investigational
PanobinostatThe serum concentration of Methyprylon can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Methyprylon can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Methyprylon can be decreased when it is combined with Peginterferon alfa-2b.Approved
PromazineThe metabolism of Methyprylon can be decreased when combined with Promazine.Approved, Vet Approved
QuinidineThe metabolism of Methyprylon can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Methyprylon can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Methyprylon can be decreased when combined with Ranolazine.Approved, Investigational
RitonavirThe metabolism of Methyprylon can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Methyprylon can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Methyprylon can be decreased when combined with Ropinirole.Approved, Investigational
SertralineThe metabolism of Methyprylon can be decreased when combined with Sertraline.Approved
StiripentolThe metabolism of Methyprylon can be decreased when combined with Stiripentol.Approved
TerbinafineThe metabolism of Methyprylon can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
ThioridazineThe metabolism of Methyprylon can be decreased when combined with Thioridazine.Approved
TiclopidineThe metabolism of Methyprylon can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Methyprylon can be decreased when combined with Tipranavir.Approved, Investigational
TranylcypromineThe metabolism of Methyprylon can be decreased when combined with Tranylcypromine.Approved
VenlafaxineThe metabolism of Methyprylon can be decreased when combined with Venlafaxine.Approved
ZiprasidoneThe metabolism of Methyprylon can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Take without regard to meals.
References
Synthesis ReferenceNot Available
General References
  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:1686463 ]
  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:2866242 ]
  3. Lomen P, Linet OI: Hypnotic efficacy of triazolam and methyprylon ininsomniac in-patients. J Int Med Res. 1976;4(1):55-8. [PubMed:16792 ]
External Links
ATC CodesN05CE02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9958
Caco-2 permeable+0.5745
P-glycoprotein substrateNon-substrate0.6409
P-glycoprotein inhibitor IInhibitor0.5252
P-glycoprotein inhibitor IINon-inhibitor0.8315
Renal organic cation transporterNon-inhibitor0.8494
CYP450 2C9 substrateNon-substrate0.8971
CYP450 2D6 substrateNon-substrate0.8024
CYP450 3A4 substrateNon-substrate0.5391
CYP450 1A2 substrateNon-inhibitor0.8306
CYP450 2C9 inhibitorNon-inhibitor0.8167
CYP450 2D6 inhibitorNon-inhibitor0.9028
CYP450 2C19 inhibitorNon-inhibitor0.8604
CYP450 3A4 inhibitorNon-inhibitor0.8925
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.922
Ames testNon AMES toxic0.7267
CarcinogenicityNon-carcinogens0.8355
BiodegradationNot ready biodegradable0.866
Rat acute toxicity2.3600 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9762
hERG inhibition (predictor II)Non-inhibitor0.9295
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
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 Solubility11.3 mg/mLALOGPS
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 Area46.17 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity50.25 m3·mol-1ChemAxon
Polarizability19.95 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-052f-9400000000-a2bf5474c5cd64d42619View in MoNA
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as piperidinediones. These are compounds containing a piperidine ring which bears two ketones.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassPiperidinones
Direct ParentPiperidinediones
Alternative Parents
Substituents
  • Piperidinedione
  • Delta-lactam
  • Cyclic ketone
  • Secondary carboxylic acid amide
  • Lactam
  • Ketone
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By si...
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
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:17139284 ]
  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:17016423 ]
  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:1352660 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein group
Organism
Human
Pharmacological action
yes
Actions
positive allosteric modulator
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Components:
NameUniProt IDDetails
Gamma-aminobutyric acid receptor subunit alpha-1P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3P28472 Details
Gamma-aminobutyric acid receptor subunit deltaO14764 Details
Gamma-aminobutyric acid receptor subunit epsilonP78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3Q99928 Details
Gamma-aminobutyric acid receptor subunit piO00591 Details
Gamma-aminobutyric acid receptor subunit thetaQ9UN88 Details
References
  1. ChEMBL Compound Report Card [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23