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Modafinil
Systematic (IUPAC) name
2-[di(phenyl)methylsulfinyl]acetamide
Identifiers
CAS number	68693-11-8
ATC code	N06BA07
PubChem	4236
DrugBank	APRD00534
Chemical data
Formula	C15H15NO2S
Mol. mass	273.35
SMILES	eMolecules & PubChem
Physical data
Melt. point	164–166 °C (327–331 °F)
Solubility in water	0.622 mg/mL (20 °C)
Pharmacokinetic data
Bioavailability	Not determined due to the aqueous insolubility
Protein binding	60%
Metabolism	Hepatic, including CYP3A4 and other pathways
Half life	10–12 hours
Excretion	Urine (as metabolites)
Therapeutic considerations
Licence data	US FDA:link
Pregnancy cat.	B3(AU) C(US)
Legal status	Prescription Only (S4)(AU) POM(UK) Schedule IV(US) ℞ Prescription only
Routes	Oral

Modafinil (Provigil/Alertec/Modavigil) is a stimulant drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration (FDA) for the treatment of narcolepsy, shift work sleep disorder,^[1] and excessive daytime sleepiness associated with obstructive sleep apnea.^[2]

Modafinil, like other stimulants, increases the release of monoamines but also elevates hypothalamic histamine levels,^[3] leading some researchers to consider Modafinil a "wakefulness promoting agent" rather than a classic amphetamine-like stimulant (as evidenced by the difference in c-fos distribution caused by modafinil as compared to amphetamine).^[4]

Although modafinil is thought to be effective in the treatment of Attention-Deficit Hyperactivity Disorder (ADHD), in 2006 it was specifically rejected by the FDA for use by children for that purpose after Cephalon was rebuffed in its effort to introduce modafinil as a children's drug under the trade name, Sparlon. Cephalon's own label for Provigil now discourages its use by children for any purpose.^[5]

Modafinil has been shown to be effective in the treatment of depression,^[6] cocaine addiction,^[7] Parkinson's Disease,^[8] schizophrenia,^[9] and disease-related fatigue.^[10][11] By law, however, Cephalon is not allowed to market Modafinil in the United States for conditions other than those officially approved by the FDA.^[12]

Modafinil and its chemical precursor adrafinil were developed by Lafon Laboratories, a French company acquired by Cephalon in 2001.^[13] Modafinil is the primary metabolite of adrafinil, and, while their activity is similar, adrafinil requires a higher dose to achieve equipotent effects. Modafinil is a racemic mixture; the (R)-enantiomer is known as armodafinil.

Contents 1 Indications 2 Off-label use 2.1 Doping agent 2.2 Multiple sclerosis 2.3 ADHD 2.4 Other uses 3 Experimental uses 3.1 Cocaine addiction 3.2 Weight loss 3.3 Primary biliary cirrhosis 3.4 Post-chemotherapy cognitive impairment 3.5 Mood elevation 4 Contraindications and warnings 4.1 Severe adverse reactions 5 Side-effects 6 Military use 7 Pharmacology 8 Pharmacokinetics 9 History 10 Other wakefulness promoting agents 11 Legal status 12 In popular culture 13 See also 14 References 15 External links

[edit] Indications

In the United States, modafinil is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, obstructive sleep apnea/hypopnea and shift work sleep disorder. In some countries, it is also approved for idiopathic hypersomnia (all forms of excessive daytime sleepiness where causes can't be established).

[edit] Off-label use

Modafinil is widely used off-label to suppress the need for sleep. It is also used off-label in combating general fatigue unrelated to lack of sleep such as in treating ADHD and as an adjunct to antidepressants (particularly in individuals with significant residual fatigue).

There is a disagreement whether the cognitive effects modafinil showed in healthy non-sleep-deprived people are sufficient to consider it to be a cognitive enhancer.^[14][15][16] The researchers agree that modafinil improves some aspects of working memory, such as digit span, digit manipulation and pattern recognition memory, but the results related to spatial memory, executive function and attention are equivocal.^{[14][15][16][17]} Some of the positive effects of modafinil may be limited to "lower-performing"^[17] individuals or to the individuals with lower IQ.^[18]

Anecdotally, many researchers in math and physics who try modafinil report a detrimental (but reversible) effect upon inductive reasoning and creativity with chronic (but not acute) use, an effect not seen with caffeine and classical amphetamines.^[19]

There is also evidence that it has neuroprotective effects.^[20]

Modafinil may be also an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression ^[21]

[edit] Doping agent

Modafinil has received some publicity in the past when several athletes were discovered allegedly using it as a performance-enhancing doping agent. It is not clear how widespread this practice is. Since there are no studies pertaining to this sort of use, it is unknown whether modafinil can have any impact on an athlete's performance. However, anecdotal evidence indicates that modafinil does indeed enhance physical performance. Modafinil was added to the World Anti-Doping Agency "Prohibited List" in 2004 as a prohibited stimulant.

[edit] Multiple sclerosis

Modafinil has been used to allay symptoms of the neurological fatigue reported by some with multiple sclerosis. Patients follow either the standard usage or take a single dose of 200–400 mg at the start of days self-assessed as being potentially excessively fatiguing. In 2000, Cephalon conducted a study to evaluate modafinil as a potential treatment for MS-related fatigue. A group of 72 people with MS of varying degrees of severity tested two different doses of modafinil and an inactive placebo over nine weeks. Fatigue levels were self-evaluated on standardized scales. Participants taking a lower dose of modafinil reported feeling less fatigued and there was a statistically significant difference in fatigue scores for the lower dose versus the placebo. The higher dose of modafinil was not reported to be significantly more effective.^[22]

[edit] ADHD

As of February 2007, there are at least seven English-language articles on randomized clinical trials in humans in the Medline database addressing the use of modafinil for the treatment of attention deficit/hyperactivity disorder (ADHD)^{[citation needed]}. Some studies have shown the use of modafinil in the treatment of ADHD is associated with significant improvements in primary outcome measures.^{[citation needed]} Cognitive function in ADHD patients was also found to improve following modafinil treatment, in some studies.^{[citation needed]} Studies for ADHD report insomnia and headache were the most common adverse effects, seen in approximately 20% of treated individuals.^{[citation needed]} These studies were not adequate to demonstrate that the beneficial effects of modafinil are maintained with chronic administration. Additional large, long-term studies using flexible titration methods to establish safety and efficacy and head-to-head comparisons between modafinil and stimulants are needed to determine the role of modafinil in the treatment of ADHD.^[23]

In December 2004, Cephalon submitted a supplemental new drug application (sNDA) to market Sparlon, a brand name of tablets containing higher doses of modafinil for the treatment of ADHD in children and adolescents ages 6 through 17. However, in March 2006, the FDA advisory committee voted 12 to 1 against approval, citing concerns about a number of reported cases of skin rash reactions in a 1000-patient trial, including one which was thought to be likely a case of Stevens-Johnson syndrome.^[24][25] Final rejection occurred in August 2006, although subsequent follow-up indicated that the skin rash reaction was not Stevens-Johnson syndrome.^{[citation needed]} Cephalon then decided to discontinue development of the Sparlon product for use in pediatric cases, though there is potential for use in treating Adult ADHD.

Modafinil is relatively contraindicated for patients with a history of cardiac events. However, one 2005 case report^[26] positively describes transitioning a 78 year old with "significant cardiac comorbidity" from methylphenidate (5 mg b.i.d.) to modafinil; however, this was in the context of severe treatment resistant depression, not ADHD.

[edit] Other uses

Modafinil is also used off-label to treat sedation and fatigue in depression,^[27][28], fibromyalgia, chronic fatigue syndrome, myotonic dystrophy,^[29] opioid-induced sleepiness,^[30] spastic cerebral palsy,^[31] and Parkinson’s disease.^[32] It increases subjective mood and friendliness, at least among shift workers.^[33]

[edit] Experimental uses

[edit] Cocaine addiction

A single 8-week double-blind study of modafinil for cocaine dependence produced inconclusive results. The number of cocaine-positive urine samples was significantly lower in the modafinil group as compared to the placebo group in the middle of the trial, but by the end of the 8 weeks the difference stopped being significant. Even before the treatment began, the modafinil group had lower cocaine consumption further confounding the results. As compared to placebo, modafinil did not reduce cocaine craving or self-reported cocaine use, and the physicians ratings were only insignificantly better.^[34] Dan Umanoff, of the National Association for the Advancement and Advocacy of Addicts, criticized the authors of the study for leaving the negative results out of the discussion part and the abstract of the article.^[35][36]

[edit] Weight loss

Studies on modafinil (even those on healthy weight individuals) indicate that it has an appetite reducing/weight loss effect.^{[37][33][38][39][40]} All studies on modafinil in the Medline database that are for one month or longer which report weight changes find that modafinil users experience weight loss compared to placebo.^[41] However, the prescribing information for Provigil notes that "There were no clinically significant differences in body weight change in patients treated with PROVIGIL compared to placebo-treated patients in the placebo-controlled clinical trials." ^[42]

In experimental studies, the appetite reducing effect of modafinil appears to be similar to that of amphetamines, but, unlike amphetamines, the dose of modafinil that is effective at decreasing food intake does not significantly increase heart rate. Also, an article published in the Annals of Clinical Psychiatry, presented the case of a 280 pound patient (BMI=35.52) who lost 40 pounds over the course of a year on Modafinil (to 30.44 BMI). After three years, his weight stabilized at a 50 pound weight loss (29.59 BMI). The authors conclude that placebo controlled studies should be conducted on using Modafinil as a weight loss agent.^[37] Conversely, a US patent (#6,455,588) on using modafinil as an appetite stimulating agent has been filed by Cephalon in 2000.

[edit] Primary biliary cirrhosis

Modafinil has been shown to improve excessive daytime somnolence and fatigue in primary biliary cirrhosis. After two months of treatment significant improvement was observed in symptoms of fatigue using the Epworth Sleepiness Scale.^[43]

[edit] Post-chemotherapy cognitive impairment

Modafinil has been used off-label in trials with people with symptoms of Post-chemotherapy cognitive impairment, also known as "chemobrain".^[44] A University of Rochester study of 68 subjects had significant results. "We knew from previous studies that modafinil does alleviate problems with memory and attention, and were hoping it would do the same for breast-cancer patients experiencing chemo-brain, which it did," related the study's lead author Sadhna Kohli, Ph.D, a research assistant professor at the University of Rochester's James P. Wilmot Cancer Center.^[45]

[edit] Mood elevation

Modafinil used in a randomized double-blind study showed that normal healthy volunteers between the ages of 30-44 showed general improvement in alertness as well as mood. In the three-day study, counterbalanced, randomized, crossover, inpatient trial of modafinil 400 mg was administered as well as a placebo to the control group. The conclusion demonstrated that modafinil may have general mood-elevating effects in particular for the adjunctive use in treatment-resistant depression.^[43]

[edit] Contraindications and warnings

Literature distributed by maker Cephalon advises that it is important to consult with your physician before using Modafinil, particularly for those with:

• Hypersensitivity to the drug or other constituents of the tablets, or
• Previous cardiovascular problems, particularly while using other stimulants, or
• Cirrhosis, or
• Cardiac conditions, particularly:
  • Left ventricular hypertrophy, or
  • Mitral valve prolapse.
    • Asymptomatic MVP is not uncommon, but neither is it prominently discussed in Modafinil's context.

Although it is not discussed in the literature, the standard binders used for Modafinil contain wheat gluten^{[citation needed]}, and so persons who have Coeliac Disease (Celiac Disease) should avoid the drug.

[edit] Severe adverse reactions

Modafinil may induce severe dermatologic reactions requiring hospitalization. From the date of initial marketing, December 1998, to January 30, 2007, FDA received six cases of severe cutaneous adverse reactions associated with modafinil, including erythema multiforme (EM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) involving adult and pediatric patients. The FDA issued a relevant alert. In the same alert, the FDA also noted that angioedema and multi-organ hypersensitivity reactions have also been reported in postmarketing experience. "Modafinil (marketed as Provigil): Serious Skin Reactions". FDA. Fall, 2007. http://www.fda.gov/cder/dsn/2007_fall/postmarketing.htm#modafinil. 

See the ADHD section for discussion of transitions to modafinil from high dose stimulant regimens. Patients with severe anxiety should be carefully supervised, as modafinil may exacerbate their condition. It may be necessary to coadminister an anxiolytic. High blood pressure should be stabilized before initiating treatment with modafinil or any other stimulant. The patient should inform the prescribing physician of any other drugs they are currently taking, as modafinil may interact with a great number of drugs.

Relatively little is known regarding safety of modafinil during pregnancy or breastfeeding. Studies on pregnant rats and rabbits suggest that high doses of modafinil during pregnancy may increase the likelihood of birth defects. There are no adequate and well controlled trials with modafinil in pregnant women. Modafinil should only be used in pregnancy if the potential benefit for the mother justifies the potential risk to the fetus. It is not known if modafinil or its metabolites are excreted in human milk. Caution should be exercised when modafinil is administered to a nursing woman. Modafinil may reduce the effectiveness of contraceptives. While some sources recommend the avoidance of alcohol in combination with modafinil, the interaction between modafinil and alcohol has not yet been studied.^[46]

[edit] Side-effects

The most common side-effects observed with modafinil, as compared to placebo, when prescribed in the recommended doses for the approved indications, are as follows:^{[citation needed]}

• Common
  • Headache (34% vs 23%)
  • Nausea (11% vs 3%)
• Less common
  • Nervousness (7% vs 3%)
  • Insomnia (5% vs 1%)
  • Anxiety (5% vs 1%)
  • Dizziness (5% vs 4%)
• Infrequent
  • Chest pain (3% vs 1%)
  • Hypertension (3% vs 1%)
  • Tachycardia (2% vs 1%)
  • Vasodilatation (2% vs 0%)
  • Dry mouth (4% vs 2%)
  • Paresthesia (2% vs 0%)
  • Pharyngitis (4% vs 2%)
  • Anorexia (4% vs 1%)

In 2007, the FDA ordered Cephalon to modify the Provigil leaflet in bold-face print of several serious and potentially fatal conditions attributed to modafinil use, including TEN, DRESS syndrome, and Stevens-Johnson Syndrome (SJS).

Additionally, gastrointestinal distress, which may be alleviated by taking the drug after a meal, aggressiveness and skin irritation have been reported, but are rare. Most side-effects subside after a few weeks without reducing the dose. Only headaches and anxiety have been shown to be proportional to dose, and these may benefit from a temporary reduction or dividing the dose. A single case of premature ventricular contractions appeared causally linked to administration of modafinil.^[47]

Modafinil may have an adverse effect on hormonal contraceptives, lasting for a month after cessation of dosage.^[48] Modafinil toxicity levels vary widely among species. In mice and rats, the median lethal dose LD₅₀ of modafinil is approximately or slightly greater than 1250 mg/kg. Oral LD₅₀ values reported for rats range from 1000 mg/kg to 3400 mg/kg. Intravenous LD₅₀ for dogs is 300 mg/kg. In clinical trials on humans, taking up to 1200 mg/day for 7 to 21 days or one-time doses up to 4500 mg did not appear to cause life-threatening effects, although a number of adverse experiences were observed, including excitation or agitation, insomnia, anxiety, irritability, aggressiveness, confusion, nervousness, tremor, palpitations, sleep disturbances, nausea, and diarrhea. As of 2004, FDA is not aware of any fatal overdoses involving modafinil alone (as opposed to multiple drugs, including modafinil).^[49] Consequently, oral LD₅₀ of modafinil in humans is not known exactly. However, it appears to be higher than oral LD₅₀ of caffeine.

[edit] Military use

Militaries of several countries are known to have expressed interest in Modafinil as an alternative for amphetamine—the drug traditionally employed in combat situations where troops face sleep deprivation, such as during lengthy missions. The French government indicated that the Foreign Legion used modafinil during certain covert operations. The United Kingdom's Ministry of Defence has admitted conducting ongoing research into Modafinil^[50] and spent £300,000 on one investigation.^[51]

In the United States military, Modafinil has been approved for use on certain Air Force missions, and it is being investigated for other uses.^[52]One study on helicopter pilots suggested that 600 mg of modafinil given in three doses can be used to keep pilots alert and maintain their accuracy at pre-deprivation levels for 40 hours without sleep.^[53] However, significant levels of nausea and vertigo were observed. Another study of fighter pilots showed that modafinil given in three divided 100 mg doses sustained the flight control accuracy of sleep-deprived F-117 pilots to within about 27 percent of baseline levels for 37 hours, without any considerable side effects.^[54] In an 88-hour sleep loss study of simulated military grounds operations, 400 mg/day doses were mildly helpful at maintaining alertness and performance of subjects compared to placebo, but the researchers concluded that this dose was not high enough to compensate for most of the effects of complete sleep loss.^[55]

[edit] Pharmacology

The exact mechanism of action of Modafinil is unclear, although numerous in vitro studies have shown it to increase the levels of various monoamines, namely; dopamine in the striatum and nucleus accumbens,^[56][57] noradrenaline in the hypothalamus and ventrolateral preoptic nucleus,^[58][59] and serotonin in the amygdala and frontal cortex.^[60] While the co-administration of a dopamine antagonist is known to decrease the stimulant effect of amphetamine, it does not negate the wakefulness-promoting actions of modafinil. Modafinil activates glutamatergic circuits while inhibiting GABAergic neurotransmission. Modafinil is thought to have less potential for abuse than other stimulants due to the absence of any significant euphoric or pleasurable effects.

The central stimulating effect of modafinil shows dose and time-related features. The effect tends to be enhanced by chlorination but reduced by methylation. Modafinil blocks the reuptake of norepinephrine by the noradrenergic terminals on sleep-promoting neurons from the ventrolateral preoptic nucleus (VLPO). Such a mechanism could be at least partially responsible for the wake-promoting effect of modafinil. Modafinil has a binding coefficient (K_i) of about 4,000 nmol/L for the dopamine reuptake transporter, and in excess of 10,000 nmol/L for the norepinephrine reuptake transporter.

A newly proposed mechanism of action involves brain peptides called orexins, also known as hypocretins. Orexin neurons are found in the hypothalamus but project to many different parts of the brain, including several areas that regulate wakefulness. Activation of these neurons increases dopamine and norepinephrine in these areas, and excite histaminergic tuberomammillary neurons increasing histamine levels there. There are two receptors for hypocretins, namely hcrt1 and hcrt2. Animal studies have shown that animals with defective orexin systems show signs and symptoms similar to narcolepsy. Modafinil seems to activate these orexin neurons thus promoting wakefulness. However, a study of genetically modified dogs lacking orexin receptors showed that modafinil still promoted wakefulness in these animals, suggesting that orexin activation is not required for the effects of modafinil.

It is possible that modafinil acts by a synergistic combination of mechanisms including direct inhibition of dopamine and norepinephrine reuptake, as well as orexin activation. It has been shown in rats that modafinil increases histamine release in the brain, and this may be a possible mechanism of action in humans.^[61]

[edit] Pharmacokinetics

Modafinil induces the cytochrome P450 enzymes CYP1A2, CYP2B6 and CYP3A4, as well as inhibiting CYP2C9 and CYP2C19 in vitro. It may also induce P-glycoprotein, which may affect drugs transported by Pgp, such as digoxin. The bioavailability of Modafinil is greater than 80% of the administered dose. In vitro measurements indicate that 60% of Modafinil is bound to plasma proteins at clinical concentrations of the drug. This percentage actually changes very little when the concentration is varied.^[62] C_max occurs approximately 2–3 hours after administration. Food will slow absorption, but does not affect the total AUC. Half-life is generally in the 10–12 hour range, subject to differences in CYP genotypes, liver function and renal function. It is metabolized in the liver, and its inactive metabolite is excreted in the urine. Urinary excretion of the unchanged drug ranges from 0% to as high as 18.7%, depending on various factors. ^[62]

[edit] History

Modafinil originated with the late 1970s invention of a series of benzhydryl sulfinyl compounds, also including adrafinil, by scientists working with the French pharmaceutical company Lafon. Adrafinil was first offered as an experimental treatment for narcolepsy in France in 1986. Modafinil is the primary metabolite of adrafinil and has similar activity but is much more widely used. It has been prescribed in France since 1994 under the name Modiodal, and in the US since 1998 as Provigil. It was approved for use in the UK in December 2002. Modafinil is marketed in the US by Cephalon Inc., who leased the rights from Lafon. Cephalon eventually purchased Lafon in 2001. In 2005, a petition by a private individual was filed with the FDA requesting over-the-counter sale of modafinil.^[63]

A U.S. Patent 4,927,855  was granted to Lafon for modafinil in 1990. The FDA granted modafinil orphan drug status in 1993. The formulation patent expired on 30 March 2006. The particle size patent was filed by Cephalon U.S. Patent 5,618,845 , covering pharmaceutical compositions of modafinil, in 1994. That patent, granted in 1997, was reissued in 2002 as RE 37,516, which provides Cephalon with patent protection for certain preparations of the drug in the United States until 2014, which is now apparently extended to April 6, 2015 after Cephalon received a six-month patent extension from the FDA.^[64] However, a settlement in which Cephalon apparently paid out US$ 200 million to four generic drug manufacturers^[65] may mean that generic forms of the drug will become available in April 2012 (October 2011 prior to the six month extension).

Some competing pharmaceutical manufacturers have applied to the FDA to market a generic form of modafinil in 2006. At least one withdrew their application after early opposition by Cephalon based on their new patent on particle sizes. There is some question as to whether a particle size patent is sufficient protection against the manufacture of generics. Pertinent questions include whether modafinil may be modified or manufactured to avoid the granularities specified in the new Cephalon patent, and whether patenting particle size is invalid because particles of appropriate sizes are likely to be obvious to practitioners skilled in the art. However, under United States patent law, a patent is entitled to a legal presumption of validity, meaning that in order to invalidate the patent, much more than "pertinent questions" are required. To date, no generic manufacturer has been able to invalidate Cephalon's particle size patent, and, indeed, those that attempted to do so were not successful such that the patent remains in force.

[edit] Other wakefulness promoting agents

Other modalities may be considered. However, Vanda Pharmaceuticals, Inc. began Phase II clinical trials in 2007 for VSF-173, a drug that also targets excessive sleepiness.^[66]

[edit] Legal status

Modafinil is currently^[update] classified as a non-narcotic Schedule IV controlled substance under United States federal law; it is illegal to import by anyone other than a DEA-registered importer without a prescription.^[67] However, one may legally bring up to 50 dosage units (i.e. pills) of Modafinil to the United States in person from a foreign country, provided that he or she has a prescription for it, and the drug is properly declared at the border crossing.^[68] Note that Adrafinil, a drug that is closely related to Modafinil, is currently not classified as a controlled substance, and therefore it is not as severely regulated.

The following countries do not classify Modafinil as a controlled substance:

• Canada (not listed in the Controlled Drugs and Substances Act, but it is a Schedule F prescription drug^[69], so it is subject to seizure by Canada Customs)
• Mexico^[70]
• United Kingdom (not listed in the Misuse of Drugs Act and is available by prescription without legal restrictions)^[71]
• Australia (listed as a Schedule 4 prescription drug)
• In Germany the classification has been changed from controlled substance (BtM) to prescription drug (RP) effective since March 1, 2008.
• In India, generic retailing as Modalert is available from Sun Pharmaceuticals.

Currently, use of modafinil is controversial in the sporting world, with high profile cases attracting press coverage as prominent United States athletes have tested positive for the substance. Some athletes who were found to have used modafinil protested that the drug was not on the prohibited list at the time of their offence. However, the World Anti-Doping Agency (WADA) maintains it was related to already banned substances. The agency added modafinil to the list of prohibited substances on August 3, 2004, ten days before the start of the 2004 Summer Olympics.

[edit] In popular culture

In the science-fiction film The Invasion, an alien virus attacks humans while they sleep, so people who want to stay alive need to stay awake. The character played by actress Nicole Kidman is seen rummaging in a pharmacy for a stimulant. She grabs a bottle of Modifinil with a 1-gram dosage (the common dosages for modafinil are 100 mg and 200 mg). In the Legacy of the Aldenata series of science fiction novels, the drug is referred to by the trade name Provigil and is used by military personnel in combination with a powerful stimulant to remain alert.

In the television series CSI: Crime Scene Investigation, the season 8 episode "Cockroaches" CSI Warrick Brown, suffering from stress-related insomnia due to his divorce, is shown taking a prescription for 100-milligram Modafinil to help him stay alert at work, but a co-worker becomes concerned that he is taking the pills too often and is taking them in conjunction with a prescription for sleeping pills (which are later referred to as Zolpidem). In the television series House, the season 2 episode "Forever" ends with a scene where Dr. Foreman is testing his memory with flash cards containing dosage information for various prescription drugs. After briefly giving up in frustration, he realizes Dr. Cameron saw him and decides to continue. Upon reading the next card, he smiles in triumph: the card is turned over to reveal the drug was Modafinil. On the Law & Order: SVU episode Hothouse a 15-year old girl used Provigil to study harder and ended up killing her roommate.

[edit] See also

• Orexin-A
• Human reliability
• Hypopnea syndrome
• Narcolepsy
• Seasonal affective disorder (SAD)
• Shift work sleep disorder (SWSD)
• Sleep apnea
• Sleep disorder
• Nootropics

[edit] References

[edit] External links

• Provigil corporate website
• "Wake Up, Little Susie" article and reporter's diary on taking modafinil from March 7, 2003 Slate magazine
• "Get ready for 24-hour living" from 18 February 2006 New Scientist
• RxList Patient Information for modafinil users
• Minzenberg, Michael J.; Cameron S. Carter (2008). "Modafinil: A Review of Neurochemical Actions and Effects on Cognition". Neuropsychopharmacology 33: 1477–502. doi:10.1038/sj.npp.1301534. 

v • d • e Stimulants Alkylamines Cyclopentamine • Geranamine • Heptaminol • Isometheptene • Octodrine • Propylhexedrine • Tuaminoheptane (Tuamine) Pyrrolidinophenones α-PPP • MDPPP • MDPV • MPBP • MPHP • MPPP • MOPPP • Pyrovalerone Cholinergics ABT-089 • ABT-418 • Anabasine • Arecoline • Cotinine • Cytisine • Dianicline • Epibatidine • Epiboxidine • GTS-21 • Ispronicline • Nicotine • Rivanicline • TC-5619 • Tebanicline • Varenicline Convulsants Bicuculline • DMCM • Flurothyl • Gabazine • Pentetrazol • Picrotoxin • Strychnine • Thujone Eugeroics Adrafinil • Armodafinil • Carphedon • Modafinil Phenethylamines 1-Phenyl-2-methylaminobutan-1-one • 2-Phenyl-3-aminobutane • 2-Phenyl-3-methylaminobutane • 4-Bromomethcathinone • 4-FA • 4-Fluoromethamphetamine • 4-Fluoromethcathinone • 4-Ethylamphetamine • 4-Hydroxyephedrine (Oxilofrine) • 4-Methylamphetamine • 4-Methylmethamphetamine • Mephedrone (4-MMC) • 4-MTA • Alfetamine • Alpha-ethyl-phenethylamine • Amfepentorex • Amphechloral • Amphetamine (Dextroamphetamine, Adderall) • Amphetaminil • Benfluorex • Benzphetamine • β-Methylphenethylamine • Bupropion • Cathinone • Chlorphentermine • Clenbuterol • Clobenzorex • Clortermine • Diethylcathinone (Diethylpropion) • Dimethoxyamphetamine • Dimethylamphetamine • Dimethylcathinone • Ephedrine • Epinephrine • Ethcathinone • Ethylamphetamine • Fenbutrazate • Fencamine • Fenethylline • Fenfluramine • Fenproporex • Fludorex • Furfenorex • Levomethamphetamine • Lisdexamfetamine • MDMA (Ecstasy) • Mefenorex • Mephentermine • Methamphetamine • Methcathinone • Methoxyphedrine • Methoxyphenamine • Methylone • Norfenefrine • Octopamine • Ortetamine • Parahydroxyamphetamine • PCA • PIA • PMA • PMEA • PMMA • PPAP • Phendimetrazine • Phenmetrazine • Phenpentermine • Phenpromethamine • Phentermine • Phenylephrine • Phenylpropanolamine • Propylamphetamine • Pseudoephedrine • Selegiline • Synephrine • Tiflorex • Xylopropamine Phenylaminooxazoles 4-Methyl-aminorex • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline • Thozalinone Piperazines 2C-B-BZP • BZP • GBR-12783 • GBR-12935 • GBR-13069 • GBR-13098 • GBR-13119 • MeOPP • MBZP • Vanoxerine Piperidines 2-Benzylpiperidine • 4-Benzylpiperidine • Desoxypipradrol • Diphemethoxidine • Ethylphenidate • HDMP-28 • (-)-Methyl-1-methyl-4β-(2-naphthyl)piperidine-3β-carboxylate • Methylphenidate (Dexmethylphenidate) • Nocaine • Phacetoperane (Levofacetoperane) • Pipradrol (Meretran) Tropanes 3α-Bis-(4-fluorophenyl)methoxytropane • 3α-((4-Chlorophenyl)phenylmethoxy)tropane • 3-Pseudotropyl-4-fluorobenzoate • Altropane (IACFT) • Brasofensine • CFT (WIN 35,428) • β-CIT (RTI-55) • Cocaethylene • Cocaine • β-CPPIT • Dichloropane (RTI-111) • Difluoropine • FE-β-CPPIT • FP-β-CPPIT • Ioflupane (FPCIT) • Norcocaine • PIT • PTT • RTI-31 • RTI-32 • RTI-51 • RTI-112 • RTI-113 • RTI-121 (IPCIT) • RTI-126 • RTI-150 • RTI-171 • RTI-177 • RTI-336 • Tesofensine • Troparil (β-CPT, WIN 35,065-2) • Tropoxane • WF-23 • WF-33 • WF-60 Xanthines Aminophylline • Caffeine • Dimethazan • Paraxanthine • Theobromine • Theophylline Others 2-Aminoindane • 5-(2-Aminopropyl)indole • Amfonelic acid • Amineptine • Amiphenazole • Bemegride • Benzydamine • BPAP • Bromantane • BTCP • BTQ • BTS 74,398 • Chlodantane • Clofenciclan • Cropropamide • Crotetamide • Cypenamine • Cyprodenate • Diclofensine • Dimethocaine • Diphenylprolinol • Etamivan • Fencamfamine • Feprosidnine • Gilutensin • GYKI-52895 • Hexacyclonate • Indanorex • Indatraline • Lefetamine • Leptacline • LR-5182 • Manifaxine • Mazindol • Meclofexonate • Mefexamide • Mesocarb • Naphthylisopropylamine • Nikethamide • Nomifensine • O-2172 • Phthalimidopropiophenone • Prolintane • Sibutramine • UH-232 • Yohimbine • Zylofuramine See also Sympathomimetic amines

v • d • e Psychoanaleptics: psychostimulants, agents used for ADHD and nootropics (N06B) Centrally acting sympathomimetics Amphetamine • Amphetaminil • Atomoxetine • Dextroamphetamine • Dextromethamphetamine • Fencamfamine • Fenozolone • Fenethylline • Methylphenidate • Mesocarb • Pemoline • Pipradrol • Prolintane Xanthine derivatives Caffeine • Propentofylline Glutamate receptor Racetams Aniracetam • Nefiracetam • Oxiracetam • Phenylpiracetam • Piracetam • Pramiracetam Ampakines CX-516 • CX-546 • CX-614 • CX-691 • CX-717 • IDRA-21 • LY-404,187 • LY-503,430 • PEPA Eugeroics / Benzhydryl compounds Adrafinil • Armodafinil • Modafinil Histamine H3 receptor antagonists A-349,821 • ABT-239 • Ciproxifan • GSK-189,254 GABAA α5 inverse agonists α5IA • L-655,708 • PWZ-029 • Suritozole Other psychostimulants and nootropics Acetylcarnitine • Adafenoxate • Bifemelane • Carbenoxolone • Citicoline • Cyprodenate • Ensaculin • Idebenone • Ispronicline • Deanol • Dimebon • Fipexide • Leteprinim • Linopirdine • Meclofenoxate • Nizofenone • Pirisudanol • Pyritinol • Sulbutiamine • Taltirelin • Tricyanoaminopropene • Vinpocetine