Identification

Name
Methyprylon
Accession Number
DB01107  (APRD00734)
Type
Small Molecule
Groups
Approved, Illicit, Withdrawn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 This medicine was used for treating insomnia, but is now rarely used as it has been replaced by newer drugs with less side effects, such as benzodiazepines. Methyprylon was withdrawn from the US market in June 1965 and the Canadian market in September 1990.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
  • Methprylon
  • Methyprolon
  • Methyprylon
  • Methyprylone
  • Methyprylonum
  • Metiprilon
  • Metiprilona
  • Metiprilone
External IDs
Dea No. 2575
International/Other Brands
Dimerin / Noctan / Nodular / Noludar
Categories
UNII
CUT48I42ON
CAS number
125-64-4
Weight
Average: 183.2475
Monoisotopic: 183.125928793
Chemical Formula
C10H17NO2
InChI Key
SIDLZWOQUZRBRU-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

Indication

For the treatment of insomnia.

Structured Indications
Not Available
Pharmacodynamics

Methyprylon, 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 action

Methyprylon 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.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
agonist
Human
AGABA-A receptor (anion channel)
positive allosteric modulator
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

60%

Metabolism

Hepatic. Methyprylon is almost completely metabolized.

Route of elimination
Not Available
Half life

6-16 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include excitation and convulsions.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not 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
DosulepinThe metabolism of Methyprylon can be decreased when combined with Dosulepin.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
ManidipineThe metabolism of Methyprylon can be decreased when combined with Manidipine.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
MidostaurinThe metabolism of Methyprylon can be decreased when combined with Midostaurin.Approved
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.Withdrawn
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

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
Human Metabolome Database
HMDB15239
KEGG Drug
D01150
PubChem Compound
4162
PubChem Substance
46506891
ChemSpider
4018
ChEBI
31837
ChEMBL
CHEMBL1200790
Therapeutic Targets Database
DAP000683
PharmGKB
PA164746748
Wikipedia
Methyprylon
ATC Codes
N05CE02 — Methyprylon

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4l-6900000000-385d8cb9bf60082827ac
Mass Spectrum (Electron Ionization)MSsplash10-052f-9400000000-a2bf5474c5cd64d42619
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as piperidinediones. These are compounds containing a piperidine ring which bears two ketones.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Piperidinones
Direct Parent
Piperidinediones
Alternative Parents
Delta lactams / Secondary carboxylic acid amides / Cyclic ketones / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Piperidinedione / Delta-lactam / Cyclic ketone / Secondary carboxylic acid amide / Lactam / Ketone / Carboxamide group / Azacycle / Carboxylic acid derivative / Organopnictogen compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not 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...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
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]

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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
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]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:52