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Modafinil

Medical Usage: – Modafinil is primarily used to treat narcolepsy, shift work sleep disorder, and obstructive sleep apnea. – Recommended as the first-choice treatment for […]

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Medical Usage:
– Modafinil is primarily used to treat narcolepsy, shift work sleep disorder, and obstructive sleep apnea.
– Recommended as the first-choice treatment for narcolepsy by sleep medicine academies in France and the US.
– Approved for adult narcolepsy in the US and for narcolepsy in children in the UK and EU.
– Considered a primary drug for narcolepsy treatment in Europe.
– Off-label use for managing fatigue in multiple sclerosis patients.

Clinical Applications:
– Off-label use of modafinil for ADHD in both children and adults.
– Adjunctive treatment in the depressive phase of bipolar disorder.
– Repurposed as an adjunctive treatment in bipolar disorder with potential cognitive benefits.
– Endorsed for off-label use in managing fatigue in multiple sclerosis.
– Used by the French Foreign Legion and in military and space contexts for its wakefulness-promoting effects.

Safety and Adverse Effects:
– Common adverse effects include headaches, nausea, reduced appetite, anxiety, and insomnia.
– Rare but serious adverse effects include severe skin rashes and allergy-related symptoms.
– No conclusive evidence of long-term safety and effectiveness.
– Low addiction and dependence liabilities compared to classical stimulants.
– Classified as a Schedule IV controlled substance with low addiction potential.

Pharmacology and Pharmacokinetics:
– Mechanism of action for narcolepsy and sleep disorders remains unclear.
– Shows low potential for causing euphoria compared to traditional stimulants.
– Peak levels occur approximately 2 to 3 hours after administration.
– Modafinil may indirectly affect norepinephrine and serotonin concentrations through dopamine activity.
– Metabolized mainly in the liver with major circulating metabolites being modafinil acid and modafinil sulfone.

Regulatory and Legal Status:
– Modafinil is classified differently across jurisdictions, such as Schedule 4 prescription-only medicine in Australia and a Class I psychotropic drug in China.
– In Canada, it is a Schedule F prescription drug.
– In Denmark, modafinil is a prescription drug but not a controlled substance.
– Legal status varies globally, with different regulations on its use and distribution.
– Modafinil is not approved for use by children in multiple jurisdictions.

Modafinil (Wikipedia)

Modafinil, sold under the brand name Provigil among others, is a wakefulness-promoting medication used primarily to treat narcolepsy. Modafinil is also approved for stimulating wakefulness in people with sleep apnea and shift work sleep disorder. It is taken by mouth. Modafinil is not approved by the US Food and Drug Administration (FDA) for use in people under age 17.

Modafinil
Clinical data
Trade namesProvigil, Alertec, Modavigil, others
Other namesCRL-40476; Diphenylmethyl-sulfinylacetamide
AHFS/Drugs.comMonograph
MedlinePlusa602016
License data
Pregnancy
category
  • AU: D
Dependence
liability
Relatively low
Addiction
liability
Low
Routes of
administration
By mouth
Drug classCNS stimulant
eugeroic
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding62.3%
MetabolismLiver (primarily via amide hydrolysis); CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5 involved
Elimination half-life12–15 h
Duration of action11.5 h
ExcretionUrine (80%)
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 has potential for causing severe allergic reactions, mental (psychiatric) effects, hypersensitivity, adverse interactions with prescription drugs, and misuse or abuse. Modafinil may harm the fetus if taken during or two months prior to pregnancy.

While modafinil is used as a cognitive enhancer or "smart drug" among healthy individuals seeking improved focus and productivity, its use outside medical supervision raises concerns regarding potential misuse or abuse. 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.

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