Methyprylon

Identification

Name
Methyprylon
Accession Number
DB01107
Description

Methyprylon is a sedative of the piperidinedione derivative family that was previously used for the treatment of insomnia. However, with the introduction of newer drugs with fewer side effects, such as benzodiazepines, the clinical use of methyprylon is now limited. Methyprylon was withdrawn from the U.S. market in June 1965 and the Canadian market in September 1990 due to adverse events.

Type
Small Molecule
Groups
Approved, Illicit, Withdrawn
Structure
Thumb
Weight
Average: 183.2475
Monoisotopic: 183.125928793
Chemical Formula
C10H17NO2
Synonyms
  • Methyprylon
  • Methyprylone
  • Methyprylonum
  • Metiprilon
  • Metiprilona
  • Metiprilone
External IDs
  • Dea No. 2575
  • Ro 1-6463

Pharmacology

Indication

For the treatment of insomnia.

Contraindications & Blackbox Warnings
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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
Humans
AGABA(A) Receptor
positive allosteric modulator
Humans
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
Adverse Effects
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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
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Methyprylon.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Methyprylon.
AclidiniumMethyprylon may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Methyprylon is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Methyprylon.
AlimemazineThe risk or severity of adverse effects can be increased when Methyprylon is combined with Alimemazine.
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Methyprylon.
AlosetronThe risk or severity of adverse effects can be increased when Alosetron is combined with Methyprylon.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Methyprylon.
AlverineThe risk or severity of adverse effects can be increased when Methyprylon is combined with Alverine.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

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International/Other Brands
Dimerin / Noctan / Noludar

Categories

ATC Codes
N05CE02 — Methyprylon
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aliphatic heteromonocyclic compound / Azacycle / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Cyclic ketone / Delta-lactam / Hydrocarbon derivative / Ketone / Lactam
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
CUT48I42ON
CAS number
125-64-4
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

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]
Human Metabolome Database
HMDB0015239
KEGG Drug
D01150
PubChem Compound
4162
PubChem Substance
46506891
ChemSpider
4018
RxNav
6910
ChEBI
31837
ChEMBL
CHEMBL1200790
Therapeutic Targets Database
DAP000683
PharmGKB
PA164746748
Wikipedia
Methyprylon

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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

Targets

Kind
Protein
Organism
Humans
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]

Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51

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