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Record Information
Version2.0
Creation Date2009-07-21 20:27:32 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2876
Identification
Common NameModafinil
ClassSmall Molecule
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.
Compound Type
  • Amide
  • Amine
  • Anorexigenic Agent
  • Appetite Depressant
  • Central Nervous System Agent
  • Central Nervous System Stimulant
  • Drug
  • Metabolite
  • Neuroprotective Agent
  • Organic Compound
  • Stimulant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Alertec
Alertex
Aspendos
Forcilin
Mentix
Modafinilo
Modafinilum
Modasomil
Modavigil
Moderateafinil
Modiodal
Provake
Provigil
Resotyl
Sparlon
Stavigile
Vigicer
Vigil
Zalux
Chemical FormulaC15H15NO2S
Average Molecular Mass273.350 g/mol
Monoisotopic Mass273.350 g/mol
CAS Registry Number68693-11-8
IUPAC Name2-diphenylmethanesulfinylacetamide
Traditional Namemodafinil
SMILESOC(=N)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1
InChI IdentifierInChI=1/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 KeyInChIKey=YFGHCGITMMYXAQ-UHFFFAOYNA-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
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point164-166°C
Boiling PointNot Available
SolubilitySlightly soluble
LogP0.6
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-014i-2900000000-528a0bbea5cbea3771e1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0390000000-c3fbad26370e7ff03677View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0560-1190000000-55b81c4a8b771b4a2bf5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-02bf-8920000000-9bdc4395d4fc1f10feaaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-2190000000-a8f51eb41df43ec99388View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-006x-8390000000-595fb55087a29048facaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05mo-9500000000-66e73e7a840f3754f786View in MoNA
Toxicity Profile
Route of ExposureRapid following oral administration.
Mechanism of ToxicityThe 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.
MetabolismHepatic 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
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIn the U.S, only for the treatment of narcolepsy, obstructive sleep apnea/hypopnea and shift work sleep disorder. In some countries, it is also approved for idiopathic hypersomnia. [Wikipedia]
Minimum Risk LevelNot Available
Health EffectsUsing large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion. Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.
SymptomsSide-effects can include sweating, dry mouth, blurred vision, insomnia, loss of appetite, and dizziness. In addition users can feel restless, anxious and moody, become excitable and have a false sense of power and security. Amphetamine overdose can also cause cardiac arrhythmias, headaches, convulsions, hypertension, rapid heart rate, coma and death. Amphetamines are psychologically and physically addictive.
TreatmentNo specific antidote to the toxic effects of modafinil overdose has been identified to date. Such overdoses should be managed with primarily supportive care, including cardiovascular monitoring. If there are no contraindications, induced emesis or gastric lavage should be considered. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00745
HMDB IDHMDB14883
PubChem Compound ID4236
ChEMBL IDCHEMBL1373
ChemSpider ID4088
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID417124
BioCyc IDNot Available
CTD IDNot Available
Stitch IDModafinil
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkModafinil
References
Synthesis Reference

DrugSyn.org

MSDSLink
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. [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. [12614915 ]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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
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. [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. [16885432 ]
  3. Swanson JM: Role of executive function in ADHD. J Clin Psychiatry. 2003;64 Suppl 14:35-9. [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. [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. [11222668 ]
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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 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. [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. [17016423 ]