Modafinil

Modafinil
Clinical data
Trade namesProvigil, Alertec, Modavigil, others
Other namesCRL-40476; CRC-40476; CEP-1538; DEP-1538; Diphenylmethyl-sulfinylacetamide
AHFS/Drugs.comMonograph
MedlinePlusa602016
License data
Pregnancy
category
Dependence
liability		Relatively low[2]
Addiction
liability		Low[2]
Routes of
administration		By mouth[3]
Drug class
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability40–65% (based on urinary excretion)[4][5]
Protein binding~60% (mainly to albumin)[4][5]
MetabolismLiver (amide hydrolysis, S-oxidation, aromatic ring hydroxylation, glucuronide conjugation; CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5 involved)[4][11][14]
Metabolites• Modafinil acid (35–65%)[4][5]
• Modafinil sulfone[4][5]
Onset of action2–4 hours (peak)[4][5]
Elimination half-lifeModafinil: 12–15 h[4][5][11]
Armodafinil: 10–17 h[12][5]
Esmodafinil: 3–5 h[4][5]
Duration of action11.5 h[13]
ExcretionUrine: 80% (≤10% as modafinil, 35–51% as modafinil acid)[12][5]
Feces: 1.0%[12]
Identifiers
  • 2-(diphenylmethanesulfinyl)acetamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.168.719 Edit this at Wikidata
Chemical and physical data
FormulaC15H15NO2S
Molar mass273.35 g·mol−1
3D model (JSmol)
  • O=S(C(c1ccccc1)c2ccccc2)CC(=O)N
  • 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) checkY
  • Key:YFGHCGITMMYXAQ-UHFFFAOYSA-N checkY
  (verify)

Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant and eugeroic (wakefulness promoter) medication used primarily to treat narcolepsy,[3][10][15] a sleep disorder characterized by excessive daytime sleepiness and sudden sleep attacks.[16] Modafinil is also approved for stimulating wakefulness in people with sleep apnea and shift work sleep disorder.[3] It is taken by mouth.[3][10] Modafinil is not approved by the US Food and Drug Administration (FDA) for use in people under 17 years old.[10]

Common side effects of Modafinil include anxiety, insomnia, dizziness, and headache. Modafinil has potential for causing severe allergic reactions, psychiatric effects,[3] hypersensitivity, adverse interactions with prescription drugs, and misuse or abuse.[3][10][15] Modafinil may harm the fetus if taken during or two months prior to pregnancy.[17]

While modafinil is used as a cognitive enhancer, or "smart drug," among healthy individuals seeking improved focus and productivity,[18][19] its use outside medical supervision raises concerns regarding potential misuse or abuse.[3][10][20] Research on the cognitive enhancement effects of modafinil in non-sleep deprived individuals has yielded mixed results, with some studies suggesting modest improvements in attention and executive functions, while others show no significant benefits or even a decline in cognitive functions at high doses.[21][22]

  1. ^ a b "TGA eBS - Product and Consumer Medicine Information Licence". Archived from the original on February 28, 2024. Retrieved February 28, 2024.
  2. ^ a b c Cite error: The named reference modafinil-schedule-IV-1999 was invoked but never defined (see the help page).
  3. ^ a b c d e f g "Modafinil Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. September 23, 2023. Archived from the original on March 30, 2019. Retrieved February 3, 2024.
  4. ^ a b c d e f g h i Sousa A, Dinis-Oliveira RJ (2020). "Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects". Subst Abus. 41 (2): 155–173. doi:10.1080/08897077.2019.1700584. PMID 31951804.
  5. ^ a b c d e f g h i j Hersey M, Tanda G (2024). "Modafinil, an atypical CNS stimulant?". Pharmacological Advances in Central Nervous System Stimulants. Adv Pharmacol. Vol. 99. pp. 287–326. doi:10.1016/bs.apha.2023.10.006. ISBN 978-0-443-21933-7. PMID 38467484.
  6. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved October 22, 2023.
  7. ^ "RDC Nº 784 – Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 – Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published April 4, 2023). March 31, 2023. Archived from the original on August 3, 2023. Retrieved August 3, 2023.
  8. ^ "Modafinil Product information". Health Canada. April 25, 2012. Archived from the original on June 10, 2022. Retrieved June 10, 2022.
  9. ^ "Modafinil Provigil 100 mg Tablets – Summary of Product Characteristics (SMPC) – (Emc)". emc. June 9, 2021. Archived from the original on December 2, 2023. Retrieved December 1, 2023.
  10. ^ a b c d e f "Provigil- modafinil tablet". DailyMed. November 30, 2018. Archived from the original on June 10, 2022. Retrieved June 10, 2022.
  11. ^ a b Robertson P, Hellriegel ET (2003). "Clinical pharmacokinetic profile of modafinil". Clinical Pharmacokinetics. 42 (2): 123–137. doi:10.2165/00003088-200342020-00002. PMID 12537513. S2CID 1266677.
  12. ^ a b c Niemegeers P, Maudens KE, Morrens M, Patteet L, Joos L, Neels H, et al. (September 2012). "Pharmacokinetic evaluation of armodafinil for the treatment of bipolar depression". Expert Opin Drug Metab Toxicol. 8 (9): 1189–1197. doi:10.1517/17425255.2012.708338. PMID 22803602.
  13. ^ Cite error: The named reference pmid22375280 was invoked but never defined (see the help page).
  14. ^ Robertson P, DeCory HH, Madan A, Parkinson A (June 2000). "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil". Drug Metabolism and Disposition. 28 (6): 664–671. PMID 10820139.
  15. ^ a b "Modafinil". MedlinePlus. US National Library of Medicine. February 15, 2016. Archived from the original on December 7, 2023. Retrieved February 3, 2024.
  16. ^ Cite error: The named reference pmid34743789 was invoked but never defined (see the help page).
  17. ^ Kaplan S, Braverman DL, Frishman I, Bartov N (February 2021). "Pregnancy and Fetal Outcomes Following Exposure to Modafinil and Armodafinil During Pregnancy". JAMA Internal Medicine. 181 (2): 275–277. doi:10.1001/jamainternmed.2020.4009. PMC 7573789. PMID 33074297.
  18. ^ Cite error: The named reference economist-2008-05-22 was invoked but never defined (see the help page).
  19. ^ Cite error: The named reference Slotnik-2017 was invoked but never defined (see the help page).
  20. ^ Greenblatt K, Adams N (February 2022). "Modafinil". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 30285371. NCBI NBK531476.
  21. ^ Cite error: The named reference pmid36056861 was invoked but never defined (see the help page).
  22. ^ Cite error: The named reference pmid32341841 was invoked but never defined (see the help page).