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Identification
NameMoricizine
Accession NumberDB00680  (APRD01124)
TypeSmall Molecule
GroupsApproved, Withdrawn
DescriptionAn antiarrhythmia agent used primarily for ventricular rhythm disturbances. [PubChem]
Structure
Thumb
Synonyms
[10-(3-Morpholin-4-yl-propionyl)-10H-phenothiazin-2-yl]-carbamic acid ethyl ester
EN-313
Ethmozin
Ethyl 10-(3-morpholinopropionyl)phenothiazine-2-carbamate
Ethyl 10-(beta-N-morpholinylpropionyl)phenothiazine-2-carbamate
Etmozin
Moracizin
Moracizina
Moracizine
Moracizinum
Moricizine
External Identifiers
  • EN-313
  • G 214
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
EthmozineNot Available
EtmozinsOlainfarm
Brand mixturesNot Available
Salts
Name/CASStructureProperties
moricizine hydrochloride
29560-58-5
Thumb
  • InChI Key: GAQAKFHSULJNAK-UHFFFAOYSA-N
  • Monoisotopic Mass: 463.1332552
  • Average Mass: 463.98
DBSALT000994
Categories
UNII2GT1D0TMX1
CAS number31883-05-3
WeightAverage: 427.517
Monoisotopic: 427.156576993
Chemical FormulaC22H25N3O4S
InChI KeyFUBVWMNBEHXPSU-UHFFFAOYSA-N
InChI
InChI=1S/C22H25N3O4S/c1-2-29-22(27)23-16-7-8-20-18(15-16)25(17-5-3-4-6-19(17)30-20)21(26)9-10-24-11-13-28-14-12-24/h3-8,15H,2,9-14H2,1H3,(H,23,27)
IUPAC Name
ethyl N-{10-[3-(morpholin-4-yl)propanoyl]-10H-phenothiazin-2-yl}carbamate
SMILES
CCOC(=O)NC1=CC2=C(SC3=CC=CC=C3N2C(=O)CCN2CCOCC2)C=C1
Pharmacology
IndicationUsed to treat irregular heartbeats (arrhythmias) and maintain a normal heart rate.
Structured Indications Not Available
PharmacodynamicsMoricizine is used to treat irregular heartbeats (arrhythmias) and to maintain a normal heart rate. It acts on the heart muscle to improve the heart's rhythm. Moricizine has potent local anesthetic activity and membrane stabilizing effect. Decreases excitability, conduction velocity, and automaticity as a result of slowed atrioventricular (AV) nodal and His-Purkinje conduction. Decreases the action potential duration (APD) in Purkinje fibers; also decreases the effective refractory period (ERP) but to a lesser extent than the APD, so the ERP/APD ratio is increased. Decreases the maxiumum rate of Phase 0 depolarization (V max ), but does not affect action potential amplitude or maximum diastolic potential. Does not affect atrial, AV nodal, or left ventricular refractory periods and has minimal effect on ventricular repolarization (evidenced by the overall decrease in JT interval). Has no effect on sinoatrial (SA) nodal or intra-atrial conduction and only minimal effect on sinus cycle length and sinus node recovery time. In the Vaughan Williams classification of antiarrhythmics, moricizine is considered to be a class I agent. It has properties of class IA, IB, and IC agents but does not clearly belong to any of the three subclasses. It has less effect on the slope of phase 0 and a greater effect on action potential duration and effective refractory period than class IC agents.
Mechanism of actionMoricizine works by inhibiting the rapid inward sodium current across myocardial cell membranes.
TargetKindPharmacological actionActionsOrganismUniProt ID
Sodium channel protein type 5 subunit alphaProteinyes
inhibitor
HumanQ14524 details
Related Articles
AbsorptionWell absorbed, absorption is complete within 2 to 3 hours. Significant first-pass metabolism results in an absolute bioavailability of approximately 38%. Administration within 30 minutes after a meal slows the rate, but does not affect the extent of absorption, although peak plasma concentrations are reduced.
Volume of distribution
  • 300 L
Protein bindingApproximately 95%.
Metabolism

Hepatic and extensive, to at least 26 metabolites, none accounting for as much as 1% of the administered dose. Two metabolites may be pharmacologically active but are present in extremely small quantities. Moricizine induces its own metabolism (it induces hepatic cytochrome P-450 activity).

Route of eliminationLess than 1% of orally administered Ethmozine® is excreted unchanged in the urine. Approximately 56% of the administered dose is excreted in the feces and 39% is excreted in the urine.
Half life2 hours (range 1.5-3.5 hours).
ClearanceNot Available
ToxicitySymptoms of overdose include vomiting, unconsciousness, and severe low blood pressure.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
5'-Deoxy-5'-MethylthioadenosineThe serum concentration of Moricizine can be increased when it is combined with 5'-Deoxy-5'-Methylthioadenosine.Experimental
AcebutololMoricizine may increase the hypotensive activities of Acebutolol.Approved
AlfentanilMoricizine may increase the hypotensive activities of Alfentanil.Approved, Illicit
AlphacetylmethadolMoricizine may increase the hypotensive activities of Alphacetylmethadol.Experimental, Illicit
AlprenololMoricizine may increase the hypotensive activities of Alprenolol.Approved, Withdrawn
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Moricizine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Aluminum phosphateAluminum phosphate can cause a decrease in the absorption of Moricizine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
AmodiaquineThe serum concentration of Moricizine can be increased when it is combined with Amodiaquine.Approved
AmoxapineThe risk or severity of adverse effects can be increased when Moricizine is combined with Amoxapine.Approved
Aop200704Moricizine may increase the hypotensive activities of Aop200704.Investigational
ArotinololMoricizine may increase the hypotensive activities of Arotinolol.Approved
ArtemetherThe serum concentration of Moricizine can be increased when it is combined with Artemether.Approved
ArtemisininThe serum concentration of Moricizine can be increased when it is combined with Artemisinin.Investigational
ArtesunateThe serum concentration of Moricizine can be increased when it is combined with Artesunate.Approved
AtenololMoricizine may increase the hypotensive activities of Atenolol.Approved
AtovaquoneThe serum concentration of Moricizine can be increased when it is combined with Atovaquone.Approved
BefunololMoricizine may increase the hypotensive activities of Befunolol.Experimental
BetaxololMoricizine may increase the hypotensive activities of Betaxolol.Approved
Betulinic AcidThe serum concentration of Moricizine can be increased when it is combined with Betulinic Acid.Investigational
BevantololMoricizine may increase the hypotensive activities of Bevantolol.Approved
BezitramideMoricizine may increase the hypotensive activities of Bezitramide.Experimental, Illicit, Withdrawn
Bismuth SubcitrateBismuth Subcitrate can cause a decrease in the absorption of Moricizine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
BisoprololMoricizine may increase the hypotensive activities of Bisoprolol.Approved
BopindololMoricizine may increase the hypotensive activities of Bopindolol.Approved
BucindololMoricizine may increase the hypotensive activities of Bucindolol.Investigational
BufuralolMoricizine may increase the hypotensive activities of Bufuralol.Experimental, Investigational
BupranololMoricizine may increase the hypotensive activities of Bupranolol.Approved
BuprenorphineMoricizine may increase the hypotensive activities of Buprenorphine.Approved, Illicit, Investigational, Vet Approved
ButorphanolMoricizine may increase the hypotensive activities of Butorphanol.Approved, Illicit, Vet Approved
Calcium carbonateCalcium carbonate can cause a decrease in the absorption of Moricizine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
CarfentanilMoricizine may increase the hypotensive activities of Carfentanil.Illicit, Vet Approved
CarteololMoricizine may increase the hypotensive activities of Carteolol.Approved
CarvedilolMoricizine may increase the hypotensive activities of Carvedilol.Approved, Investigational
CeliprololMoricizine may increase the hypotensive activities of Celiprolol.Approved, Investigational
ChloroquineThe serum concentration of Moricizine can be increased when it is combined with Chloroquine.Approved, Vet Approved
CitalopramThe risk or severity of adverse effects can be increased when Moricizine is combined with Citalopram.Approved
ClomipramineThe risk or severity of adverse effects can be increased when Moricizine is combined with Clomipramine.Approved, Vet Approved
CodeineMoricizine may increase the hypotensive activities of Codeine.Approved, Illicit
DapoxetineThe risk or severity of adverse effects can be increased when Moricizine is combined with Dapoxetine.Investigational
DapsoneThe serum concentration of Moricizine can be increased when it is combined with Dapsone.Approved, Investigational
DextromoramideMoricizine may increase the hypotensive activities of Dextromoramide.Experimental, Illicit
DextropropoxypheneMoricizine may increase the hypotensive activities of Dextropropoxyphene.Approved, Illicit, Withdrawn
DezocineMoricizine may increase the hypotensive activities of Dezocine.Approved
DihydroartemisininThe serum concentration of Moricizine can be increased when it is combined with Dihydroartemisinin.Approved
DihydrocodeineMoricizine may increase the hypotensive activities of Dihydrocodeine.Approved, Illicit
DihydroetorphineMoricizine may increase the hypotensive activities of Dihydroetorphine.Experimental, Illicit
DihydromorphineMoricizine may increase the hypotensive activities of Dihydromorphine.Experimental, Illicit
DiphenoxylateMoricizine may increase the hypotensive activities of Diphenoxylate.Approved, Illicit
DoxycyclineThe serum concentration of Moricizine can be increased when it is combined with Doxycycline.Approved, Investigational, Vet Approved
DPDPEMoricizine may increase the hypotensive activities of DPDPE.Investigational
EscitalopramThe risk or severity of adverse effects can be increased when Moricizine is combined with Escitalopram.Approved, Investigational
EsmololMoricizine may increase the hypotensive activities of Esmolol.Approved
EthylmorphineMoricizine may increase the hypotensive activities of Ethylmorphine.Approved, Illicit
EtoperidoneThe risk or severity of adverse effects can be increased when Moricizine is combined with Etoperidone.Approved
EtorphineMoricizine may increase the hypotensive activities of Etorphine.Illicit, Vet Approved
FenfluramineThe risk or severity of adverse effects can be increased when Moricizine is combined with Fenfluramine.Illicit, Withdrawn
FentanylMoricizine may increase the hypotensive activities of Fentanyl.Approved, Illicit, Investigational, Vet Approved
FluoxetineThe risk or severity of adverse effects can be increased when Moricizine is combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe risk or severity of adverse effects can be increased when Moricizine is combined with Fluvoxamine.Approved, Investigational
HalofantrineThe serum concentration of Moricizine can be increased when it is combined with Halofantrine.Approved
HeroinMoricizine may increase the hypotensive activities of Heroin.Approved, Illicit
HydrocodoneMoricizine may increase the hypotensive activities of Hydrocodone.Approved, Illicit
HydromorphoneMoricizine may increase the hypotensive activities of Hydromorphone.Approved, Illicit
HydroxychloroquineThe serum concentration of Moricizine can be increased when it is combined with Hydroxychloroquine.Approved
IndalpineThe risk or severity of adverse effects can be increased when Moricizine is combined with Indalpine.Investigational, Withdrawn
IndenololMoricizine may increase the hypotensive activities of Indenolol.Withdrawn
KetobemidoneMoricizine may increase the hypotensive activities of Ketobemidone.Approved
LabetalolMoricizine may increase the hypotensive activities of Labetalol.Approved
LevobunololMoricizine may increase the hypotensive activities of Levobunolol.Approved
Levomethadyl AcetateMoricizine may increase the hypotensive activities of Levomethadyl Acetate.Approved
LevomilnacipranThe risk or severity of adverse effects can be increased when Moricizine is combined with Levomilnacipran.Approved
LevorphanolMoricizine may increase the hypotensive activities of Levorphanol.Approved
LofentanilMoricizine may increase the hypotensive activities of Lofentanil.Illicit
Lu AA21004The risk or severity of adverse effects can be increased when Moricizine is combined with Lu AA21004.Investigational
LumefantrineThe serum concentration of Moricizine can be increased when it is combined with Lumefantrine.Approved
MagaldrateMagaldrate can cause a decrease in the absorption of Moricizine resulting in a reduced serum concentration and potentially a decrease in efficacy.Withdrawn
Magnesium carbonateMagnesium carbonate can cause a decrease in the absorption of Moricizine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Magnesium hydroxideMagnesium hydroxide can cause a decrease in the absorption of Moricizine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Magnesium oxideMagnesium oxide can cause a decrease in the absorption of Moricizine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Magnesium TrisilicateMagnesium Trisilicate can cause a decrease in the absorption of Moricizine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
MefloquineThe serum concentration of Moricizine can be increased when it is combined with Mefloquine.Approved
MethadoneMoricizine may increase the hypotensive activities of Methadone.Approved
Methadyl AcetateMoricizine may increase the hypotensive activities of Methadyl Acetate.Approved, Illicit
MetipranololMoricizine may increase the hypotensive activities of Metipranolol.Approved
MetoprololMoricizine may increase the hypotensive activities of Metoprolol.Approved, Investigational
MilnacipranThe risk or severity of adverse effects can be increased when Moricizine is combined with Milnacipran.Approved
MizoribineThe serum concentration of Moricizine can be increased when it is combined with Mizoribine.Investigational
MorphineMoricizine may increase the hypotensive activities of Morphine.Approved, Investigational
NadololMoricizine may increase the hypotensive activities of Nadolol.Approved
NalbuphineMoricizine may increase the hypotensive activities of Nalbuphine.Approved
NormethadoneMoricizine may increase the hypotensive activities of Normethadone.Approved, Illicit
OlanzapineThe risk or severity of adverse effects can be increased when Moricizine is combined with Olanzapine.Approved, Investigational
OpiumMoricizine may increase the hypotensive activities of Opium.Approved, Illicit
OxprenololMoricizine may increase the hypotensive activities of Oxprenolol.Approved
OxycodoneMoricizine may increase the hypotensive activities of Oxycodone.Approved, Illicit, Investigational
OxymorphoneMoricizine may increase the hypotensive activities of Oxymorphone.Approved, Investigational, Vet Approved
ParoxetineThe risk or severity of adverse effects can be increased when Moricizine is combined with Paroxetine.Approved, Investigational
PenbutololMoricizine may increase the hypotensive activities of Penbutolol.Approved, Investigational
PentazocineMoricizine may increase the hypotensive activities of Pentazocine.Approved, Vet Approved
PethidineMoricizine may increase the hypotensive activities of Pethidine.Approved
PindololMoricizine may increase the hypotensive activities of Pindolol.Approved
PiritramideMoricizine may increase the hypotensive activities of Piritramide.Investigational
PractololMoricizine may increase the hypotensive activities of Practolol.Approved
PrimaquineThe serum concentration of Moricizine can be increased when it is combined with Primaquine.Approved
ProguanilThe serum concentration of Moricizine can be increased when it is combined with Proguanil.Approved
PropranololMoricizine may increase the hypotensive activities of Propranolol.Approved, Investigational
PyrimethamineThe serum concentration of Moricizine can be increased when it is combined with Pyrimethamine.Approved, Vet Approved
PyronaridineThe serum concentration of Moricizine can be increased when it is combined with Pyronaridine.Investigational
QuinacrineThe serum concentration of Moricizine can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Moricizine can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Moricizine can be increased when it is combined with Quinine.Approved
RadicicolThe serum concentration of Moricizine can be increased when it is combined with Radicicol.Experimental
RemifentanilMoricizine may increase the hypotensive activities of Remifentanil.Approved
SertralineThe risk or severity of adverse effects can be increased when Moricizine is combined with Sertraline.Approved
SinefunginThe serum concentration of Moricizine can be increased when it is combined with Sinefungin.Experimental
SotalolMoricizine may increase the hypotensive activities of Sotalol.Approved
SufentanilMoricizine may increase the hypotensive activities of Sufentanil.Approved, Investigational
SulfadoxineThe serum concentration of Moricizine can be increased when it is combined with Sulfadoxine.Approved
SulfametopyrazineThe serum concentration of Moricizine can be increased when it is combined with Sulfametopyrazine.Approved, Withdrawn
tafenoquineThe serum concentration of Moricizine can be increased when it is combined with tafenoquine.Investigational
TapentadolMoricizine may increase the hypotensive activities of Tapentadol.Approved
ThiopentalThe risk or severity of adverse effects can be increased when Moricizine is combined with Thiopental.Approved, Vet Approved
TimololMoricizine may increase the hypotensive activities of Timolol.Approved
TramadolMoricizine may increase the hypotensive activities of Tramadol.Approved, Investigational
TrazodoneThe risk or severity of adverse effects can be increased when Moricizine is combined with Trazodone.Approved, Investigational
TrimethoprimThe serum concentration of Moricizine can be increased when it is combined with Trimethoprim.Approved, Vet Approved
VilazodoneThe risk or severity of adverse effects can be increased when Moricizine is combined with Vilazodone.Approved
VortioxetineThe risk or severity of adverse effects can be increased when Moricizine is combined with Vortioxetine.Approved
ZimelidineThe risk or severity of adverse effects can be increased when Moricizine is combined with Zimelidine.Withdrawn
Food InteractionsNot Available
References
Synthesis Reference

DrugSyn.org

US3740395A
General ReferencesNot Available
External Links
ATC CodesC01BG01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9885
Blood Brain Barrier+0.9535
Caco-2 permeable-0.5796
P-glycoprotein substrateSubstrate0.6871
P-glycoprotein inhibitor IInhibitor0.9072
P-glycoprotein inhibitor IINon-inhibitor0.5751
Renal organic cation transporterNon-inhibitor0.8329
CYP450 2C9 substrateNon-substrate0.7472
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5274
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.6367
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7638
Ames testNon AMES toxic0.6915
CarcinogenicityNon-carcinogens0.9153
BiodegradationNot ready biodegradable0.8412
Rat acute toxicity2.4731 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9229
hERG inhibition (predictor II)Inhibitor0.732
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Shire development inc
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point156-157 °CPhysProp
water solubility0.457 mg/LNot Available
logP2.98SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0339 mg/mLALOGPS
logP3.04ALOGPS
logP3.07ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)12.9ChemAxon
pKa (Strongest Basic)6.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.11 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity118.88 m3·mol-1ChemAxon
Polarizability45.27 Å3ChemAxon
Number of Rings4ChemAxon
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Diarylthioether
  • Beta amino acid or derivatives
  • Phenylcarbamate
  • Benzenoid
  • Oxazinane
  • Morpholine
  • Para-thiazine
  • Tertiary carboxylic acid amide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Thioether
  • Monocarboxylic acid or derivatives
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

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. 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. Ahmmed GU, Hisatome I, Kurata Y, Makita N, Tanaka Y, Tanaka H, Okamura T, Sonoyama K, Furuse Y, Kato M, Yamamoto Y, Ogura K, Shimoyama M, Miake J, Sasaki N, Ogino K, Igawa O, Yoshida A, Shigemasa C: Analysis of moricizine block of sodium current in isolated guinea-pig atrial myocytes. Atrioventricular difference of moricizine block. Vascul Pharmacol. 2002 Mar;38(3):131-41. [PubMed:12402511 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on December 08, 2016 11:46