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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2022-03-07 02:51:46 UTC
HMDB IDHMDB0014883
Secondary Accession Numbers
  • HMDB14883
Metabolite Identification
Common NameModafinil
DescriptionModafinil 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
Data?1582753231
Synonyms
ValueSource
ProvigilKegg
2-[(Diphenylmethyl)sulphinyl]acetamideGenerator
ModerateafinilHMDB
2-((Diphenylmethyl)sulfinyl)acetamideMeSH, HMDB
AlertecMeSH, HMDB
Merckle brand OF modafinilMeSH, HMDB
Cephalon brand OF modafinilMeSH, HMDB
Cephalon brand OF modafinil, reformulatedMeSH, HMDB
VigilMeSH, HMDB
BenzhydrylsulfinylacetamideMeSH, HMDB
CEPA brand OF modafinilMeSH, HMDB
Lafon brand OF modafinilMeSH, HMDB
ModiodalMeSH, HMDB
Nourypharma brand OF modafinilMeSH, HMDB
SparlonMeSH, HMDB
Draxis brand OF modafinilMeSH, HMDB
ModafinilMeSH
R-ModafinilMeSH, HMDB
NuvigilMeSH, HMDB
2-((R)-(Diphenylmethyl)sulfinyl)acetamideMeSH, HMDB
ArmodafinilMeSH, HMDB
R ModafinilMeSH, HMDB
Chemical FormulaC15H15NO2S
Average Molecular Weight273.35
Monoisotopic Molecular Weight273.082349419
IUPAC Name2-diphenylmethanesulfinylacetamide
Traditional Namemodafinil
CAS Registry Number68693-11-8
SMILES
NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1
InChI Identifier
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)
InChI KeyYFGHCGITMMYXAQ-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Benzyl alkyl sulfoxide
  • Benzyl sulfoxide
  • Carboxamide group
  • Primary carboxylic acid amide
  • Sulfoxide
  • Sulfinyl compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Carbonyl group
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point164 - 166 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.62 g/LNot Available
LogP0.6Not Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.62 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity77.39 m³·mol⁻¹ChemAxon
Polarizability28.71 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+163.70631661259
DarkChem[M-H]-158.50731661259
DeepCCS[M+H]+158.50230932474
DeepCCS[M-H]-156.14430932474
DeepCCS[M-2H]-189.0330932474
DeepCCS[M+Na]+164.59530932474
AllCCS[M+H]+162.232859911
AllCCS[M+H-H2O]+158.532859911
AllCCS[M+NH4]+165.632859911
AllCCS[M+Na]+166.632859911
AllCCS[M-H]-163.232859911
AllCCS[M+Na-2H]-163.132859911
AllCCS[M+HCOO]-163.032859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
ModafinilNC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C14144.0Standard polar33892256
ModafinilNC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C12323.5Standard non polar33892256
ModafinilNC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C12446.0Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Modafinil,1TMS,isomer #1C[Si](C)(C)NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C12404.2Semi standard non polar33892256
Modafinil,1TMS,isomer #1C[Si](C)(C)NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C12359.4Standard non polar33892256
Modafinil,1TMS,isomer #1C[Si](C)(C)NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C13154.6Standard polar33892256
Modafinil,2TMS,isomer #1C[Si](C)(C)N(C(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1)[Si](C)(C)C2413.0Semi standard non polar33892256
Modafinil,2TMS,isomer #1C[Si](C)(C)N(C(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1)[Si](C)(C)C2464.4Standard non polar33892256
Modafinil,2TMS,isomer #1C[Si](C)(C)N(C(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1)[Si](C)(C)C2983.0Standard polar33892256
Modafinil,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C12567.9Semi standard non polar33892256
Modafinil,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C12529.6Standard non polar33892256
Modafinil,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C13204.0Standard polar33892256
Modafinil,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(C(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1)[Si](C)(C)C(C)(C)C2837.4Semi standard non polar33892256
Modafinil,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(C(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1)[Si](C)(C)C(C)(C)C2856.2Standard non polar33892256
Modafinil,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(C(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1)[Si](C)(C)C(C)(C)C3076.9Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Modafinil GC-MS (Non-derivatized) - 70eV, Positivesplash10-014i-2900000000-528a0bbea5cbea3771e12017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Modafinil GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Modafinil GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Modafinil 35V, Positive-QTOFsplash10-014i-0900000000-e85eba164d5df6d6552e2021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 10V, Positive-QTOFsplash10-00di-0390000000-c3fbad26370e7ff036772016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 20V, Positive-QTOFsplash10-0560-1190000000-55b81c4a8b771b4a2bf52016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 40V, Positive-QTOFsplash10-02bf-8920000000-9bdc4395d4fc1f10feaa2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 10V, Negative-QTOFsplash10-00di-2190000000-a8f51eb41df43ec993882016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 20V, Negative-QTOFsplash10-006x-8390000000-595fb55087a29048faca2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 40V, Negative-QTOFsplash10-05mo-9500000000-66e73e7a840f3754f7862016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 10V, Positive-QTOFsplash10-014i-0900000000-c692fb05e504a5da303a2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 20V, Positive-QTOFsplash10-014i-0900000000-c692fb05e504a5da303a2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 40V, Positive-QTOFsplash10-014i-0900000000-1fe50a8d9579a6198a362021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 10V, Negative-QTOFsplash10-024i-0190000000-06b6e8449d4102829ac22021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 20V, Negative-QTOFsplash10-0udi-7900000000-4df9193e933f8acc3b4b2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Modafinil 40V, Negative-QTOFsplash10-03di-9310000000-7866ba7c4275aa6d34a02021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00745 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00745 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4088
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID77585
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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 ]
  2. 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 ]

Enzymes

General function:
Involved in monooxygenase 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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 ]
General function:
Involved in monooxygenase 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
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 ]
General function:
Involved in monooxygenase 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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
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 ]
General function:
Involved in monooxygenase 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
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 ]
General function:
Involved in monooxygenase 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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
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 ]
General function:
Involved in monooxygenase 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
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 ]
General function:
Involved in neurotransmitter:sodium symporter 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
Molecular weight:
68494.255
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular weight:
56835.4
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. 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 ]