Identification

Name
Modafinil
Accession Number
DB00745  (APRD00534)
Type
Small Molecule
Groups
Approved, Investigational
Description

Modafinil is a stimulant drug marketed as a 'wakefulness promoting agent' and is one of the stimulants used in the treatment of narcolepsy. Narcolepsy is caused by dysfunction of a family of wakefulness-promoting and sleep-suppressing peptides, the orexins, whose neurons are activated by modafinil. The prexin neuron activation is associated with psychoactivation and euphoria. The exact mechanism of action is unclear, although in vitro studies have shown it to inhibit the reuptake of dopamine by binding to the dopamine reuptake pump, and lead to an increase in extracellular dopamine. Modafinil activates glutamatergic circuits while inhibiting GABA.

Structure
Thumb
Synonyms
  • 2-((diphenylmethyl)sulfinyl)acetamide
  • Modafinil
  • Modafinilo
  • Modafinilum
  • Moderateafinil
External IDs
CEP 1538 / CEP-1538 / CRC-40476 / CRL 40476 / CRL-40476 / DEP-1538
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AlertecTablet100 mgOralTeva1999-03-24Not applicableCanada
ProvigilTablet200 mg/1OralCaremark L.L.C.2007-12-172013-06-30Us
ProvigilTablet100 mg/1OralCephalon1999-02-15Not applicableUs
ProvigilTablet200 mg/1Oralbryant ranch prepack1999-02-15Not applicableUs63629 161120180907 15195 ce40t8
ProvigilTablet200 mg/1OralRebel Distributors2004-01-19Not applicableUs63459 0201 30 nlmimage10 36429b14
ProvigilTablet100 mg/1OralPhysicians Total Care, Inc.2005-06-03Not applicableUs63459 0101 30 nlmimage10 dd1c6e93
ProvigilTablet100 mg/1OralCardinal Health1998-12-242012-02-29Us55154 097520180913 8702 71bw23
ProvigilTablet100 mg/1Oralbryant ranch prepack1998-12-24Not applicableUs63629 338820180907 15195 18kory2
ProvigilTablet200 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2011-07-20Not applicableUs
ProvigilTablet200 mg/1OralPhysicians Total Care, Inc.2004-01-19Not applicableUs54868 489720180907 15195 18gqket
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-modafinilTablet100 mgOralApotex Corporation2008-05-01Not applicableCanada
Auro-modafinilTablet100 mgOralAuro Pharma Inc2014-10-24Not applicableCanada
Bio-modafinilTablet100 mgOralBiomed Pharma2015-10-06Not applicableCanada
Ipg-modafinilTablet100 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Mar-modafinilTablet100 mgOralMarcan Pharmaceuticals Inc2015-01-09Not applicableCanada
ModafinilTablet200 mg/1Oralbryant ranch prepack2012-09-27Not applicableUs
ModafinilTablet100 mg/1OralAlembic Pharmaceuticals Inc.2017-06-30Not applicableUs
ModafinilTablet100 mg/1OralPar Pharmaceutical2012-04-06Not applicableUs
ModafinilTablet200 mg/1OralActavis Pharma Company2013-04-03Not applicableUs
ModafinilTablet100 mg/1OralHeritage2018-05-08Not applicableUs
International/Other Brands
Alertex (Saval) / Aspendos (Medochemie) / Forcilin (LKM) / Mentix (Royal Pharma) / Modasomil (Cephalon) / Modavigil (CSL) / Modiodal (Cephalon) / Provake (Ranbaxy) / Resotyl (Drugtech) / Sparlon (Cephalon) / Stavigile (Libbs) / Vigicer (Beta) / Vigil (Cephalon) / Zalux
Categories
UNII
R3UK8X3U3D
CAS number
68693-11-8
Weight
Average: 273.35
Monoisotopic: 273.082349419
Chemical Formula
C15H15NO2S
InChI Key
YFGHCGITMMYXAQ-UHFFFAOYSA-N
InChI
InChI=1S/C15H15NO2S/c16-14(17)11-19(18)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15H,11H2,(H2,16,17)
IUPAC Name
2-diphenylmethanesulfinylacetamide
SMILES
NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

To improve wakefulness in patients with excessive daytime sleepiness (EDS) associated with narcolepsy.

Associated Conditions
Pharmacodynamics

Modafinil is a stimulant drug marketed as a 'wakefulness promoting agent' and is one of the stimulants used in the treatment of narcolepsy. Narcolepsy is caused by dysfunction of a family of wakefulness-promoting and sleep-suppressing peptides, the orexins, whose neurons are activated by modafinil. The prexin neuron activation is associated with psychoactivation and euphoria. Modafinil is not indicated for complaints of lack of energy or fatigue; but it appears to be very helpful for some patients. Also, it has been used in the treatment of hypersomnia, a disorder in which patients lack the capacity for meaningful sleep and may require ten or more hours per day. Recent studies have have found that modafinil may help recovering cocaine addicts fight their addiction.

Mechanism of action

The exact mechanism of action is unclear, although in vitro studies have shown it to inhibit the reuptake of dopamine by binding to the dopamine reuptake pump, and lead to an increase in extracellular dopamine. Modafinil activates glutamatergic circuits while inhibiting GABA. Modafinil is thought to have less potential for abuse than other stimulants due to the absence of any significant euphoric or pleasurable effects. It is possible that modafinil acts by a synergistic combination of mechanisms including direct inhibition of dopamine reuptake, indirect inhibition of noradrenalin reuptake in the VLPO and orexin activation. Modafinil has partial alpha 1B-adrenergic agonist effects by directly stimulating the receptors.

TargetActionsOrganism
ASodium-dependent dopamine transporter
inhibitor
Human
UAlpha-1B adrenergic receptor
partial agonist
Human
Absorption

Rapid following oral administration.

Volume of distribution
  • 0.9 L/kg
Protein binding

60%

Metabolism

Hepatic

Route of elimination

The major route of elimination is metabolism (~90%), primarily by the liver, with subsequent renal elimination of the metabolites.

Half life

23-215 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Catechol O-methyltransferase---(A;A)AA alleleEffect Directly StudiedPatients with this genotype have reduced improvement in vigor and well-being with modafinil.Details
Catechol O-methyltransferase---(G;G)GG alleleEffect Directly StudiedPatients with this genotype have increased improvement in vigor and well-being with modafinil.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Modafinil.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Modafinil.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Modafinil.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Modafinil.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Modafinil.
6-Deoxyerythronolide BThe metabolism of Modafinil can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Modafinil.
8-azaguanineThe metabolism of 8-azaguanine can be increased when combined with Modafinil.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be increased when combined with Modafinil.
9-DeazaguanineThe metabolism of 9-Deazaguanine can be increased when combined with Modafinil.
Food Interactions
  • Take without regard to meals.

References

Synthesis Reference
US4177290
General References
  1. Lindsay SE, Gudelsky GA, Heaton PC: Use of modafinil for the treatment of attention deficit/hyperactivity disorder. Ann Pharmacother. 2006 Oct;40(10):1829-33. Epub 2006 Sep 5. [PubMed:16954326]
  2. Ishizuka T, Sakamoto Y, Sakurai T, Yamatodani A: Modafinil increases histamine release in the anterior hypothalamus of rats. Neurosci Lett. 2003 Mar 20;339(2):143-6. [PubMed:12614915]
External Links
Human Metabolome Database
HMDB0014883
KEGG Drug
D01832
PubChem Compound
4236
PubChem Substance
46504648
ChemSpider
4088
BindingDB
50156055
ChEBI
77585
ChEMBL
CHEMBL1373
PharmGKB
PA450530
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Modafinil
ATC Codes
N06BA07 — Modafinil
AHFS Codes
  • 28:20.80 — Wakefulness-promoting Agents
FDA label
Download (98.9 KB)
MSDS
Download (57 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentPostural Tachycardia Syndrome1
0CompletedBasic ScienceHealthy Volunteers / Moods Disorders / Substance-Related Disorders1
0CompletedSupportive CareFluid Inteligence / Healthy Young Subjects / Modafinil / Resting State Networks1
0CompletedTreatmentCannabis / Marijuana Abuse1
0Enrolling by InvitationTreatmentParkinson's Disease (PD)1
1Active Not RecruitingBasic ScienceCognitive Symptom / Schizophrenic Disorders1
1Active Not RecruitingOtherHealthy Volunteers1
1Active Not RecruitingTreatmentEwing's Sarcoma (ES) / Liver Cancer / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedNot AvailableAutonomic Failure / Idiopathic orthostatic hypotension1
1CompletedNot AvailableCocaine Abuse / Dependence, Cocaine / Substance Abuse1
1CompletedNot AvailableCognitive Impairments1
1CompletedNot AvailableHealthy Volunteers3
1CompletedBasic ScienceHealthy Volunteers1
1CompletedHealth Services ResearchCognitively Healthy Subjects Influenced by Psychoactive Drugs1
1CompletedOtherSchizoaffective Disorders / Schizophrenic Disorders1
1CompletedTreatmentMalignant Melanoma / Melanoma / Recurrent Melanoma1
1CompletedTreatmentPrimary Biliary Cholangitis / Tiredness1
1CompletedTreatmentSleep Apnea Syndrome1
1CompletedTreatmentSleep Deprivation1
1CompletedTreatmentTiredness1
1CompletedTreatmentTobacco Use Disorders1
1RecruitingTreatmentDependence, Cocaine1
1TerminatedTreatmentTinnitus1
1Unknown StatusTreatmentAmphetamine-Related Disorders1
1Unknown StatusTreatmentCocaine-Related Disorders / Drug Administration Schedule / Intravenous Infusions1
1, 2Active Not RecruitingTreatmentChronic Orthostatic Intolerance / Tachycardia1
1, 2CompletedTreatmentSchizophrenia and Schizophrenia Spectrum Psychosis1
1, 2WithdrawnSupportive CareLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingTreatmentCancer of the Ovary1
2Active Not RecruitingTreatmentCancer of the Ovary / Neoplasms, Ovarian1
2Active Not RecruitingTreatmentEwing's Sarcoma (ES)1
2CompletedDiagnosticCocaine-Related Disorders1
2CompletedOtherCocaine Related Disorders1
2CompletedSupportive CareBrain and Central Nervous System Tumors / Cognitive/Functional Effects / Neurologic toxicity / Psychosocial Effects of Cancer and Its Treatment / Tiredness1
2CompletedTreatmentAlcohol Dependence / Alcohol-Related Disorders / Cocaine-Related Disorders1
2CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
2CompletedTreatmentCocaine-Related Disorders2
2CompletedTreatmentDependence, Cocaine5
2CompletedTreatmentMajor Depressive Disorder (MDD)1
2CompletedTreatmentCancer treatment / Malignancies / Tiredness1
2CompletedTreatmentMethamphetamine Addiction1
2CompletedTreatmentMethamphetamine Dependence4
2CompletedTreatmentNarcolepsy1
2CompletedTreatmentNeglect / Spatial Neglect / Swallowing Disorders1
2Enrolling by InvitationTreatmentCancer of the Ovary / Cancer, Breast / Cervical Cancers / Endometrial Cancers / Fallopian Tube Cancer / Primary Peritoneal Carcinoma / Triple Negative Breast Cancer (TNBC) / Uterine Malignancies1
2RecruitingTreatmentAdvanced Gynecological Cancers / Cancer of the Ovary / Cervical Cancers / Uterine Malignancies1
2RecruitingTreatmentAlcohol Use Disorder (AUD)1
2RecruitingTreatmentCocaine-Related Disorders1
2RecruitingTreatmentNarcolepsy1
2RecruitingTreatmentAcute, recurrent Myeloid Leukemia / Refractory Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
2TerminatedSupportive CareCentral Nervous System Tumor, Pediatric / Specific Disorders of Sleep / Tiredness1
2TerminatedTreatmentExcessive Daytime Sleepiness / Hypopnoea Syndrome / Sleep Apnea, Obstructive1
2TerminatedTreatmentMethamphetamine Dependence1
2TerminatedTreatmentTiredness1
2Unknown StatusTreatmentAmphetamine Dependence1
2Unknown StatusTreatmentAmphetamine Dependence / Substance Dependence1
2Unknown StatusTreatmentCocaine Abuse / Cocaine-Related Disorders1
2Unknown StatusTreatmentCocaine Abuse / Opiate Dependence1
2Unknown StatusTreatmentDependence, Cocaine1
2WithdrawnBasic ScienceDepression1
2WithdrawnTreatmentAdvanced Non-Small Cell Lung Cancer / Metastatic Non-Small Cell Lung Cancer / Neoplasms, Lung1
2WithdrawnTreatmentParkinson's Disease (PD)1
2WithdrawnTreatmentSchizophrenic Disorders1
2, 3CompletedTreatmentAtypical Depression1
2, 3Unknown StatusTreatmentPosttraumatic Stress Disorders1
3CompletedSupportive CareCancer Related Fatigue / Quality of Life1
3CompletedSupportive CareTiredness / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedTreatmentAlzheimer's Disease (AD) / Apathy1
3CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)2
3CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Attention Deficit/Hyperactivity Disorder1
3CompletedTreatmentCancer, Breast / Prostatic Neoplasms1
3CompletedTreatmentCataplexy / Excessive Daytime Sleepiness / Narcolepsy1
3CompletedTreatmentCataplexy / Excessive Daytime Sleepiness / Narcolepsy / Sleep disorders and disturbances1
3CompletedTreatmentChronic Shift Work Sleep Disorder1
3CompletedTreatmentDependence, Cocaine1
3CompletedTreatmentNarcolepsy3
3CompletedTreatmentNarcolepsy / Sleep Apnea, Obstructive1
3CompletedTreatmentSleep Apnea, Obstructive1
3CompletedTreatmentTreatment of Excessive Daytime Sleepiness in Narcolepsy1
3Not Yet RecruitingTreatmentCognitive Impairments / Major Depressive Disorder (MDD)1
3RecruitingTreatmentEwing Family of Tumors / Ewing's Sarcoma (ES) / Ewing's Tumor Metastatic / Metastatic Ewing's Sarcoma1
3RecruitingTreatmentFatigue in Multiple Sclerosis1
3TerminatedTreatmentMalignancies / Pain NOS1
3TerminatedTreatmentNeoplasms, Brain1
3TerminatedTreatmentPost Stroke Fatigue / Strokes1
3TerminatedTreatmentPostpoliomyelitis Syndrome1
3Unknown StatusSupportive CareExcessive Sleepiness / Malignancies / Pain Palliation1
3WithdrawnTreatmentDelirium / Respiratory Failure1
4CompletedBasic ScienceOsteoarthritis (OA)1
4CompletedTreatmentAttention / Executive Function / Memory, Short-Term1
4CompletedTreatmentBipolar Disorder (BD)1
4CompletedTreatmentDelayed Emergence From Anesthesia / Obstructive Sleep Apnea (OSA)1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tiredness1
4CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
4CompletedTreatmentMajor Depressive Disorder (MDD) / Mental Health1
4CompletedTreatmentMethamphetamine Dependence1
4CompletedTreatmentObstructive Sleep Apnea Syndrome (OSAS)1
4CompletedTreatmentPrimary Insomnia1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
4CompletedTreatmentSchizophrenic Disorders2
4CompletedTreatmentTiredness1
4Not Yet RecruitingTreatmentDisseminated Sclerosis1
4Not Yet RecruitingTreatmentRespiratory Insufficiency1
4RecruitingTreatmentAcute Agitation / Aggressive Behavior / Psychiatric Emergency1
4RecruitingTreatmentTiredness1
4TerminatedTreatmentAlzheimer's Disease (AD) / Sleep Initiation and Maintenance Disorders / Sleeplessness1
4TerminatedTreatmentHealthy Volunteers1
4Unknown StatusTreatmentSchizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
Not AvailableCompletedNot AvailableDependence, Cocaine / Substance-induced Cognitive Disorder / Substance-induced Sleep Disorder1
Not AvailableCompletedBasic ScienceCognitive Performance / Creativity / Healthy Volunteers / Motivation / Reward / Subjective Pleasure1
Not AvailableCompletedBasic ScienceHealthy Volunteers2
Not AvailableCompletedDiagnosticHypersomnia / Narcolepsy1
Not AvailableCompletedPreventionWeight gain therapy1
Not AvailableCompletedSupportive CareBrain and Central Nervous System Tumors / Cognitive/Functional Effects / Tiredness1
Not AvailableCompletedTreatmentCataplexy / Excessive Sleepiness / Hypersomnolence / Narcolepsy / Sleep disorders and disturbances1
Not AvailableCompletedTreatmentDependence, Cocaine1
Not AvailableCompletedTreatmentDisseminated Sclerosis1
Not AvailableCompletedTreatmentImpaired Glucose Metabolism / Sleep Restriction1
Not AvailableCompletedTreatmentSchizophrenic Disorders1
Not AvailableRecruitingNot AvailableAlcohol Dependence / Cocaine Abuse / Dependence, Cocaine / Opiate Dependence / Substance Abuse1
Not AvailableRecruitingNot AvailableNarcolepsy / Obstructive Sleep Apnea (OSA) / Shift-work related sleep disturbance1
Not AvailableRecruitingBasic ScienceHealthy Volunteers1
Not AvailableSuspendedTreatmentCocaine-Related Disorders / Opioid-Related Disorders1
Not AvailableTerminatedTreatmentSystemic Lupus Erythematosus (SLE)1
Not AvailableUnknown StatusSupportive CareCognitive/Functional Effects / Depression / Tiredness / Unspecified Adult Solid Tumor, Protocol Specific1
Not AvailableUnknown StatusTreatmentAll Multiple Sclerosis Patients1
Not AvailableUnknown StatusTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
Not AvailableUnknown StatusTreatmentSevere Traumatic Brain Injury / Traumatic Brain Injury (TBI)1
Not AvailableWithdrawnTreatmentParkinson's Disease (PD)1

Pharmacoeconomics

Manufacturers
  • Cephalon inc
  • Cephalon, Inc.
Packagers
  • Bryant Ranch Prepack
  • Caremark LLC
  • Cephalon Inc.
  • Cima Laboratories Inc.
  • DispenseXpress Inc.
  • Diversified Healthcare Services Inc.
  • DSM Corp.
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Resource Optimization and Innovation LLC
  • Shire Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral100 mg/1
TabletOral200 mg/1
Prices
Unit descriptionCostUnit
Provigil 200 mg tablet15.33USD tablet
Provigil 100 mg tablet13.58USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
USRE37516No2002-01-152014-10-06Us
CA2165824No2005-08-022014-06-14Canada
CA2201967No2002-12-102015-10-04Canada
US7297346Yes2007-11-202024-05-29Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)164-166 °CNot Available
water solubilitySlightly solubleNot Available
logP0.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.622 mg/mLALOGPS
logP1.75ALOGPS
logP1.53ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)8.84ChemAxon
pKa (Strongest Basic)-4.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.16 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity77.39 m3·mol-1ChemAxon
Polarizability28.71 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9947
Caco-2 permeable+0.5066
P-glycoprotein substrateNon-substrate0.8912
P-glycoprotein inhibitor INon-inhibitor0.8842
P-glycoprotein inhibitor IINon-inhibitor0.9962
Renal organic cation transporterNon-inhibitor0.8153
CYP450 2C9 substrateNon-substrate0.793
CYP450 2D6 substrateNon-substrate0.8659
CYP450 3A4 substrateNon-substrate0.5971
CYP450 1A2 substrateNon-inhibitor0.6653
CYP450 2C9 inhibitorNon-inhibitor0.6045
CYP450 2D6 inhibitorNon-inhibitor0.9117
CYP450 2C19 inhibitorNon-inhibitor0.6952
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6395
Ames testNon AMES toxic0.6562
CarcinogenicityNon-carcinogens0.6665
BiodegradationReady biodegradable0.6304
Rat acute toxicity2.0926 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9799
hERG inhibition (predictor II)Non-inhibitor0.9279
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
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 diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Benzyl alkyl sulfoxides / Sulfoxides / Primary carboxylic acid amides / Sulfinyl compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Diphenylmethane / Benzyl alkyl sulfoxide / Benzyl sulfoxide / Carboxamide group / Primary carboxylic acid amide / Sulfoxide / Sulfinyl compound / Carboxylic acid derivative / Hydrocarbon derivative / Carbonyl group
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid amide, sulfoxide (CHEBI:77585)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Zhou J, He R, Johnson KM, Ye Y, Kozikowski AP: Piperidine-based nocaine/modafinil hybrid ligands as highly potent monoamine transporter inhibitors: efficient drug discovery by rational lead hybridization. J Med Chem. 2004 Nov 18;47(24):5821-4. [PubMed:15537337]
  2. Madras BK, Xie Z, Lin Z, Jassen A, Panas H, Lynch L, Johnson R, Livni E, Spencer TJ, Bonab AA, Miller GM, Fischman AJ: Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro. J Pharmacol Exp Ther. 2006 Nov;319(2):561-9. Epub 2006 Aug 2. [PubMed:16885432]
  3. Swanson JM: Role of executive function in ADHD. J Clin Psychiatry. 2003;64 Suppl 14:35-9. [PubMed:14658934]
  4. Dopheide MM, Morgan RE, Rodvelt KR, Schachtman TR, Miller DK: Modafinil evokes striatal [(3)H]dopamine release and alters the subjective properties of stimulants. Eur J Pharmacol. 2007 Jul 30;568(1-3):112-23. Epub 2007 Apr 5. [PubMed:17477916]
  5. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM: Dopaminergic role in stimulant-induced wakefulness. J Neurosci. 2001 Mar 1;21(5):1787-94. [PubMed:11222668]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Chen CR, Qu WM, Qiu MH, Xu XH, Yao MH, Urade Y, Huang ZL: Modafinil exerts a dose-dependent antiepileptic effect mediated by adrenergic alpha1 and histaminergic H1 receptors in mice. Neuropharmacology. 2007 Sep;53(4):534-41. Epub 2007 Jun 30. [PubMed:17681557]

Enzymes

Details
1. Cytochrome P450 2C19
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 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. Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [PubMed:10820139]
  3. Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [PubMed:12537513]
  4. Modafinil FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
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. Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [PubMed:12537513]
  2. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 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. Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [PubMed:12537513]
  3. Alan H.B. Wu (2006). Tietz Clinical Guide to Laboratory Tests. Elsevier.
  4. Pharmacogenomics Table [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 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. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [PubMed:10820139]
  2. Robertson P Jr, Hellriegel ET, Arora S, Nelson M: Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers. J Clin Pharmacol. 2002 Feb;42(2):205-14. [PubMed:11831544]
  3. Modafinil FDA [File]
  4. Modafinil EMA label [File]
  5. Modafinil FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
Inducer
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 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. Robertson P Jr, Hellriegel ET, Arora S, Nelson M: Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Clin Pharmacol Ther. 2002 Jan;71(1):46-56. [PubMed:11823757]
  3. Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [PubMed:10820139]

Drug created on June 13, 2005 07:24 / Updated on November 16, 2018 11:11