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Identification
NameQuinidine barbiturate
Accession NumberDB01346
TypeSmall Molecule
GroupsApproved
DescriptionThe 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
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNIINot Available
CAS numberNot Available
WeightAverage: 556.652
Monoisotopic: 556.268570282
Chemical FormulaC32H36N4O5
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassCinchona alkaloids
Sub ClassNot Available
Direct ParentCinchona alkaloids
Alternative Parents
Substituents
  • Cinchonan-skeleton
  • Hydroxyquinoline
  • Quinoline
  • Barbiturate
  • Quinuclidine
  • Anisole
  • Aralkylamine
  • Ureide
  • Pyrimidone
  • Alkyl aryl ether
  • Benzenoid
  • Pyrimidine
  • Pyridine
  • Piperidine
  • 1,3-diazinane
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Urea
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Carboxamide group
  • 1,2-aminoalcohol
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationNot Available
PharmacodynamicsNot Available
Mechanism of actionBarbiturates 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot 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. 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. 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
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 protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is respon...
Gene Name:
SCN5A
Uniprot ID:
Q14524
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 (PubMed:15820677, PubMed:21653227). Forms dimeric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel is selective for K(+) ions at physiological potass...
Gene Name:
KCNK1
Uniprot ID:
O00180
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 neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and t...
Gene Name:
GRIA2
Uniprot ID:
P42262
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 ]
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Drug created on June 30, 2007 12:14 / Updated on August 17, 2016 12:23