Quinidine barbiturate

Identification

Name
Quinidine barbiturate
Accession Number
DB01346
Type
Small Molecule
Groups
Approved
Description

The administration of quinidine derivatives helps to observe various skin and mucosal reactions. A papulopurpuric eruption in a patient (without thrombopenia) can be developed who is taking quinidine phenylethyl barbiturate intermittently and at reintroduction.(PMID: 9739909)

Structure
Thumb
Synonyms
Not Available
Categories
Not Available
UNII
Not Available
CAS number
Not Available
Weight
Average: 556.652
Monoisotopic: 556.268570282
Chemical Formula
C32H36N4O5
InChI Key
YHRUERMOPBDCFD-UHFFFAOYSA-N
InChI
InChI=1S/C20H24N2O2.C12H12N2O3/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18;1-2-12(8-6-4-3-5-7-8)9(15)13-11(17)14-10(12)16/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3;3-7H,2H2,1H3,(H2,13,14,15,16,17)
IUPAC Name
5-ethyl-5-phenyl-1,3-diazinane-2,4,6-trione; {5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl}(6-methoxyquinolin-4-yl)methanol
SMILES
CCC1(C(=O)NC(=O)NC1=O)C1=CC=CC=C1.COC1=CC2=C(C=CN=C2C=C1)C(O)C1CC2CCN1CC2C=C

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Barbiturates work by binding to the GABAA receptor at either the alpha or the beta sub unit. These are binding sites that are distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. This GABAA receptor binding decreases input resistance, depresses burst and tonic firing, especially in ventrobasal and intralaminar neurons, while at the same time increasing burst duration and mean conductance at individual chloride channels; this increases both the amplitude and decay time of inhibitory postsynaptic currents. In addition to this GABA-ergic effect, barbiturates also block the AMPA receptor, a subtype of glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
potentiator
Human
AGamma-aminobutyric acid receptor subunit alpha-2
potentiator
Human
ASodium channel protein type 5 subunit alpha
inhibitor
Human
UPotassium channel subfamily K member 1
inhibitor
Human
UGlutamate receptor 2
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15436
PubChem Compound
53461739
PubChem Substance
46504552
ChemSpider
26329517
Therapeutic Targets Database
DAP000915
PharmGKB
PA164783957

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
Not Available
Predicted Properties
PropertyValueSource
logP2.51ChemAxon
pKa (Strongest Acidic)13.89ChemAxon
pKa (Strongest Basic)9.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area45.59 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity94.69 m3·mol-1ChemAxon
Polarizability35.97 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9643
Blood Brain Barrier-0.8743
Caco-2 permeable-0.6288
P-glycoprotein substrateSubstrate0.8932
P-glycoprotein inhibitor IInhibitor0.6667
P-glycoprotein inhibitor IIInhibitor0.5351
Renal organic cation transporterNon-inhibitor0.749
CYP450 2C9 substrateNon-substrate0.7463
CYP450 2D6 substrateNon-substrate0.8209
CYP450 3A4 substrateSubstrate0.6175
CYP450 1A2 substrateNon-inhibitor0.8637
CYP450 2C9 inhibitorNon-inhibitor0.7258
CYP450 2D6 inhibitorNon-inhibitor0.898
CYP450 2C19 inhibitorNon-inhibitor0.7931
CYP450 3A4 inhibitorNon-inhibitor0.5314
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6681
Ames testNon AMES toxic0.6774
CarcinogenicityNon-carcinogens0.8584
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7298 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8436
hERG inhibition (predictor II)Inhibitor0.6121
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 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 cinchona alkaloids. These are alkaloids structurally characterized by the presence of the cinchonan skeleton, which consists of a quinoline linked to an azabicyclo[2.2.2]octane moiety.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Cinchona alkaloids
Sub Class
Not Available
Direct Parent
Cinchona alkaloids
Alternative Parents
4-quinolinemethanols / Barbituric acid derivatives / Anisoles / Quinuclidines / Aralkylamines / Alkyl aryl ethers / N-acyl ureas / Diazinanes / Benzene and substituted derivatives / Pyridines and derivatives
show 12 more
Substituents
Cinchonan-skeleton / 4-quinolinemethanol / Quinoline / Barbiturate / Anisole / Quinuclidine / Alkyl aryl ether / N-acyl urea / Pyrimidone / Aralkylamine
show 31 more
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
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. Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. [PubMed:14579514]
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [PubMed:10209232]
  3. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [PubMed:10487207]
  4. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [PubMed:11264449]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  6. Stobbs SH, Ohran AJ, Lassen MB, Allison DW, Brown JE, Steffensen SC: Ethanol suppression of ventral tegmental area GABA neuron electrical transmission involves N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 2004 Oct;311(1):282-9. Epub 2004 May 28. [PubMed:15169831]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA2
Uniprot ID
P47869
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-2
Molecular Weight
51325.85 Da
References
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [PubMed:11264449]
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [PubMed:10209232]
  3. Stobbs SH, Ohran AJ, Lassen MB, Allison DW, Brown JE, Steffensen SC: Ethanol suppression of ventral tegmental area GABA neuron electrical transmission involves N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 2004 Oct;311(1):282-9. Epub 2004 May 28. [PubMed:15169831]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Stokoe KS, Thomas G, Goddard CA, Colledge WH, Grace AA, Huang CL: Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/Delta murine hearts modelling long QT syndrome 3. J Physiol. 2007 Jan 1;578(Pt 1):69-84. Epub 2006 Oct 5. [PubMed:17023504]
  2. Itoh H, Shimizu M, Takata S, Mabuchi H, Imoto K: A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs. J Cardiovasc Electrophysiol. 2005 May;16(5):486-93. [PubMed:15877619]
  3. Grant AO: Electrophysiological basis and genetics of Brugada syndrome. J Cardiovasc Electrophysiol. 2005 Sep;16 Suppl 1:S3-7. [PubMed:16138883]
  4. Napolitano C, Priori SG: Brugada syndrome. Orphanet J Rare Dis. 2006 Sep 14;1:35. [PubMed:16972995]
  5. Ohgo T, Okamura H, Noda T, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S, Ohe T, Shimizu W: Acute and chronic management in patients with Brugada syndrome associated with electrical storm of ventricular fibrillation. Heart Rhythm. 2007 Jun;4(6):695-700. Epub 2007 Feb 20. [PubMed:17556186]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Sheets MF, Fozzard HA, Lipkind GM, Hanck DA: Sodium channel molecular conformations and antiarrhythmic drug affinity. Trends Cardiovasc Med. 2010 Jan;20(1):16-21. doi: 10.1016/j.tcm.2010.03.002. [PubMed:20685573]
  8. Tella SR, Goldberg SR: Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine. Pharmacol Biochem Behav. 1998 Feb;59(2):305-12. [PubMed:9476974]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium channel activity
Specific Function
Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues (PubMe...
Gene Name
KCNK1
Uniprot ID
O00180
Uniprot Name
Potassium channel subfamily K member 1
Molecular Weight
38142.775 Da
References
  1. Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J: TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J. 1996 Mar 1;15(5):1004-11. [PubMed:8605869]
  2. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Lazdunski M: Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J. 1996 Dec 16;15(24):6854-62. [PubMed:9003761]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Ionotropic glutamate receptor activity
Specific Function
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory ne...
Gene Name
GRIA2
Uniprot ID
P42262
Uniprot Name
Glutamate receptor 2
Molecular Weight
98820.32 Da
References
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [PubMed:11264449]
  2. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [PubMed:10487207]
  3. Stobbs SH, Ohran AJ, Lassen MB, Allison DW, Brown JE, Steffensen SC: Ethanol suppression of ventral tegmental area GABA neuron electrical transmission involves N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 2004 Oct;311(1):282-9. Epub 2004 May 28. [PubMed:15169831]

Drug created on June 30, 2007 12:14 / Updated on November 09, 2017 02:59