Identification

Name
Prochlorperazine
Accession Number
DB00433  (APRD00624)
Type
Small Molecule
Groups
Approved, Vet approved
Description

A phenothiazine antipsychotic used principally in the treatment of nausea; vomiting; and vertigo. It is more likely than chlorpromazine to cause extrapyramidal disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p612)

Structure
Thumb
Synonyms
  • 2-Chloro-10-(3-(1-methyl-4-piperazinyl)propyl)-phenothiazine
  • 2-Chloro-10-(3-(4-methyl-1-piperazinyl)propyl)phenothiazine
  • 3-Chloro-10-(3-(1-methyl-4-piperazinyl)propyl)phenothiazine
  • 3-Chloro-10-(3-(4-methyl-1-piperazinyl)propyl)phenothiazine
  • Capazine
  • Chlormeprazine
  • Chloro-3 (N-methylpiperazinyl-3 propyl)-10 phenothiazine
  • Chloropernazine
  • Emetiral
  • N-(gamma-(4'-Methylpiperazinyl-1')propyl)-3-chlorophenothiazine
  • Prochlorperazin
  • Prochlorpérazine
  • Prochlorperazinum
  • Prochlorpermazine
  • Prochlorpromazine
  • Procloperazine
  • Proclorperazina
External IDs
Bayer A 173 / RP 6140 / SKF 4657
Product Ingredients
IngredientUNIICASInChI Key
Prochlorperazine dimaleateNot AvailableNot AvailableNot applicable
Prochlorperazine edisylatePG20W5VQZS1257-78-9SWOUGRBFXFILIB-UHFFFAOYSA-N
Prochlorperazine maleateI1T8O1JTL684-02-6DSKIOWHQLUWFLG-SPIKMXEPSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CompazineTablet, coated5 mg/1OralGlaxosmithkline Inc2006-02-022011-02-11Us
CompazineSyrup5 mg/5mLOralGlaxoSmithKline2006-05-112006-05-11Us
CompazineCapsule, extended release15 mg/1OralGlaxoSmithKline2006-05-112006-05-11Us
CompazineInjection, solution5 mg/1mmIntramuscular; IntravenousGlaxoSmithKline2006-05-112006-05-11Us
CompazineTablet, coated5 mg/1OralPhysicians Total Care, Inc.1956-10-232004-12-31Us
CompazineCapsule, extended release10 mg/1OralGlaxoSmithKline2006-05-112006-05-11Us
CompazineSuppository5 mg/1RectalGlaxoSmithKline2006-05-112006-05-11Us
CompazineSuppository25 mg/1RectalPhysicians Total Care, Inc.1993-06-222011-05-31Us
CompazineInjection, solution5 mg/1mmIntramuscular; IntravenousGlaxoSmithKline2006-05-112006-05-11Us
CompazineTablet, coated10 mg/1OralPhysicians Total Care, Inc.1956-10-232004-12-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CompazineTablet, film coated5 mg/1OralPbm Pharmaceuticals Inc.2014-04-012015-12-31Us
CompazineSuppository25 mg/1RectalPbm Pharmaceuticals Inc.2013-07-01Not applicableUs
CompazineTablet, film coated10 mg/1OralPbm Pharmaceuticals Inc.2014-04-012016-01-31Us
ComproSuppository25 mg/1RectalA-S Medication Solutions2000-09-01Not applicableUs
ComproSuppository25 mg/1RectalPD-Rx Pharmaceuticals, Inc.2000-09-01Not applicableUs
ComproSuppository25 mg/1RectalPaddock Laboratories, LLC2000-09-01Not applicableUs
Nu-prochlor Tab 10mgTablet10 mgOralNu Pharm Inc1992-12-312012-09-04Canada
Nu-prochlor Tab 5mgTablet5 mgOralNu Pharm Inc1992-12-312012-09-04Canada
PMS-prochlorperazine Suppositoires 10mgSuppository10 mgRectalPharmascience Inc1989-12-31Not applicableCanada
PMS-prochlorperazine Tab 10mgTablet10 mgOralPharmascience Inc1989-12-31Not applicableCanada
International/Other Brands
Buccastem (Reckitt Benckiser) / Emetiral (Zentiva) / Stemzine (Sanofi-Aventis) / Volimin (Chin Teng)
Categories
UNII
YHP6YLT61T
CAS number
58-38-8
Weight
Average: 373.943
Monoisotopic: 373.13794618
Chemical Formula
C20H24ClN3S
InChI Key
WIKYUJGCLQQFNW-UHFFFAOYSA-N
InChI
InChI=1S/C20H24ClN3S/c1-22-11-13-23(14-12-22)9-4-10-24-17-5-2-3-6-19(17)25-20-8-7-16(21)15-18(20)24/h2-3,5-8,15H,4,9-14H2,1H3
IUPAC Name
2-chloro-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine
SMILES
CN1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(Cl)C=C3)CC1

Pharmacology

Indication

For the symptomatic management of psychotic disorders, short term management of nonpsychotic anxiety in patients with generalized anxiety disorder, and for the control of severe nausea and vomiting of various causes.

Associated Conditions
Pharmacodynamics

Prochlorperazine is a piperazine phenothiazine related to high-potency neuroleptics such as perphenazine. It shares many of the actions and adverse effects of the antipsychotics.

Mechanism of action

The mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its antidopaminergic effects. Prochlorperazine blocks the D2 somatodendritic autoreceptor, resulting in the blockade of postsynaptic dopamine receptors in the mesolimbic system and an increased dopamine turnover. Prochlorperazine also has anti-emetic effects, which can be attributed to dopamine blockade in the chemoreceptor trigger zone. Prochlorperazine also blocks anticholinergic and alpha-adrenergic receptors, the blockade of alpha(1)-adrenergic receptors resulting in sedation, muscle relaxation, and hypotension.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
Absorption

Rapidly absorbed following oral administration

Volume of distribution
Not Available
Protein binding

91-99%

Metabolism

Hepatic. Undergoes metabolism in the gastric mucosa and on first pass through the liver, CYP2D6 and/or CYP3A4.

Route of elimination
Not Available
Half life

6 to 8 hours

Clearance
Not Available
Toxicity

Symptoms of central nervous system depression to the point of somnolence or coma. Agitation and restlessness may also occur. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever and autonomic reactions such as hypotension, dry mouth and ileus; LD50=400mg/kg (orally in mice)

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Prochlorperazine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Prochlorperazine.
2,5-Dimethoxy-4-ethylamphetamineProchlorperazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineProchlorperazine may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Prochlorperazine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Prochlorperazine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Prochlorperazine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with 4-Methoxyamphetamine.
Food Interactions
  • Avoid alcohol.
  • Take with a full glass of water Avoid excessive quantities of coffee or tea (Caffeine).
  • Take with food.

References

Synthesis Reference
US2902484
General References
Not Available
External Links
Human Metabolome Database
HMDB0014577
KEGG Drug
D00493
KEGG Compound
C07403
PubChem Compound
4917
PubChem Substance
46509018
ChemSpider
4748
BindingDB
78434
ChEBI
8435
ChEMBL
CHEMBL728
Therapeutic Targets Database
DAP000373
PharmGKB
PA451114
HET
P77
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Prochlorperazine
ATC Codes
N05AB04 — Prochlorperazine
AHFS Codes
  • 56:22.08 — Antihistamines
  • 28:16.08.24 — Phenothiazines
PDB Entries
3m0w
FDA label
Download (617 KB)
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMigraines1
2CompletedTreatmentNausea and vomiting1
2TerminatedTreatmentBenign Headache1
3Active Not RecruitingTreatmentMigraine Disorders1
3CompletedSupportive CareNausea1
3CompletedSupportive CareNausea and vomiting / Unspecified Adult Solid Tumor, Protocol Specific1
3RecruitingSupportive CareCarcinoma, Breast1
3TerminatedTreatmentHeadaches1
4CompletedTreatmentHeadaches1
4CompletedTreatmentMigraines2
4RecruitingPreventionLaparoscopic Sleeve Gastrectomy / Post-Operative Nausea and Vomiting (PONV)1
4RecruitingTreatmentHeadaches1
4TerminatedTreatmentMigrainous Headache1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1
Not AvailableCompletedTreatmentAcute Migraine Headache1
Not AvailableUnknown StatusSupportive CareNon-Hodgkin's Lymphoma (NHL)1

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
  • Paddock laboratories inc
  • Able laboratories inc
  • G and w laboratories inc
  • Alpharma us pharmaceuticals division
  • Morton grove pharmaceuticals inc
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Marsam pharmaceuticals llc
  • Smith and nephew solopak div smith and nephew
  • Teva parenteral medicines inc
  • Watson laboratories inc
  • Wyeth ayerst laboratories
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Cadista pharmaceuticals inc
Packagers
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Barr Pharmaceuticals
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bryant Ranch Prepack
  • Cadista Pharmaceuticals Inc.
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • G & W Labs
  • General Injectables and Vaccines Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hospira Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Liberty Pharmaceuticals
  • Medisca Inc.
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Paddock Labs
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Patient First Corp.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharma Pac LLC
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
Capsule, extended releaseOral10 mg/1
Capsule, extended releaseOral15 mg/1
Injection, solutionIntramuscular; Intravenous5 mg/1mm
SuppositoryRectal2.5 mg/1
SuppositoryRectal5 mg/1
SyrupOral5 mg/5mL
Tablet, coatedOral10 mg/1
Tablet, coatedOral5 mg/1
SuppositoryRectal10 mg
TabletOral10 mg
TabletOral5 mg
SuppositoryRectal25 mg/1
InjectionIntramuscular5 mg/1mL
InjectionIntramuscular; Intravenous5 mg/1mL
Injection, solutionIntramuscular; Intravenous5 mg/1mL
TabletOral10 mg/1
TabletOral5 mg/61
TabletOral5 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral5 mg/1
LiquidIntramuscular; Intravenous5 mg
SolutionIntramuscular; Intravenous5 mg
SyrupOral5 mg
Prices
Unit descriptionCostUnit
Prochlorperazine mal powder4.77USD g
Compazine 25 mg suppository4.25USD suppository
Prochlorperazine 25 mg suppository3.13USD suppository
Compro 25 mg suppository3.05USD suppository
Compazine 5 mg tablet1.82USD tablet
Compazine 10 mg tablet1.8USD tablet
Prochlorperazine 5 mg/ml vial1.22USD ml
Prochlorperazine 5 mg/ml0.91USD ml
Prochlorperazine Maleate 10 mg tablet0.88USD tablet
Sandoz Prochlorperazine 10 mg Suppository0.87USD suppository
Prochlorperazine 10 mg tablet0.85USD tablet
Prochlorperazine Maleate 5 mg tablet0.59USD tablet
Prochlorperazine 5 mg tablet0.57USD tablet
Apo-Prochlorazine 10 mg Tablet0.21USD tablet
Apo-Prochlorazine 5 mg Tablet0.17USD tablet
Novamine 15% iv solution0.09USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)228 °CPhysProp
water solubility15 mg/L (at 24 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.88HANSCH,C ET AL. (1995)
logS-4.4ADME Research, USCD
pKa8.1SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.011 mg/mLALOGPS
logP4.67ALOGPS
logP4.38ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)8.39ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.72 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity109.81 m3·mol-1ChemAxon
Polarizability41.77 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9821
Blood Brain Barrier+0.9781
Caco-2 permeable+0.7729
P-glycoprotein substrateSubstrate0.8537
P-glycoprotein inhibitor IInhibitor0.817
P-glycoprotein inhibitor IIInhibitor0.8577
Renal organic cation transporterInhibitor0.7615
CYP450 2C9 substrateNon-substrate0.7702
CYP450 2D6 substrateNon-substrate0.5179
CYP450 3A4 substrateNon-substrate0.5346
CYP450 1A2 substrateInhibitor0.9376
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.9723
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.7676
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8557
Ames testNon AMES toxic0.8999
CarcinogenicityNon-carcinogens0.9456
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3496 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8165
hERG inhibition (predictor II)Inhibitor0.786
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (10.4 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-01vo-9853000000-ba88fedd94e150c34e1a
GC-MS Spectrum - EI-BGC-MSsplash10-0229-7933000000-4e14a9a9728c361941d3
Mass Spectrum (Electron Ionization)MSsplash10-022c-9752000000-533ac31876b44d82f2aa
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00fr-0219000000-abf2f9a1f6a1efb497b8

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Alkyldiarylamines / Diarylthioethers / N-methylpiperazines / Benzenoids / Aryl chlorides / 1,4-thiazines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organochlorides
show 1 more
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Tertiary aliphatic/aromatic amine / N-alkylpiperazine / N-methylpiperazine / Para-thiazine / Aryl chloride / Aryl halide
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, organochlorine compound, N-alkylpiperazine, N-methylpiperazine (CHEBI:8435)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Roberge RJ: Antiemetic-related dystonic reaction unmasked by removal of a scopolamine transdermal patch. J Emerg Med. 2006 Apr;30(3):299-302. [PubMed:16677982]
  3. Hamik A, Peroutka SJ: Differential interactions of traditional and novel antiemetics with dopamine D2 and 5-hydroxytryptamine3 receptors. Cancer Chemother Pharmacol. 1989;24(5):307-10. [PubMed:2527092]
  4. Vinson DR: Development of a simplified instrument for the diagnosis and grading of akathisia in a cohort of patients receiving prochlorperazine. J Emerg Med. 2006 Aug;31(2):139-45. [PubMed:17044574]
  5. Callan JE, Kostic MA, Bachrach EA, Rieg TS: Prochlorperazine vs. promethazine for headache treatment in the emergency department: a randomized controlled trial. J Emerg Med. 2008 Oct;35(3):247-53. doi: 10.1016/j.jemermed.2007.09.047. Epub 2008 Jun 5. [PubMed:18534808]
  6. Narita M, Takei D, Shiokawa M, Tsurukawa Y, Matsushima Y, Nakamura A, Takagi S, Asato M, Ikegami D, Narita M, Amano T, Niikura K, Hashimoto K, Kuzumaki N, Suzuki T: Suppression of dopamine-related side effects of morphine by aripiprazole, a dopamine system stabilizer. Eur J Pharmacol. 2008 Dec 14;600(1-3):105-9. doi: 10.1016/j.ejphar.2008.10.030. Epub 2008 Oct 21. [PubMed:18955042]
  7. Golembiewski J, Tokumaru S: Pharmacological prophylaxis and management of adult postoperative/postdischarge nausea and vomiting. J Perianesth Nurs. 2006 Dec;21(6):385-97. [PubMed:17169748]

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]
  2. Davies SJ, Eayrs S, Pratt P, Lennard MS: Potential for drug interactions involving cytochromes P450 2D6 and 3A4 on general adult psychiatric and functional elderly psychiatric wards. Br J Clin Pharmacol. 2004 Apr;57(4):464-72. doi: 10.1111/j.1365-2125.2003.02040.x. [PubMed:15025745]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 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 December 12, 2018 07:04