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Encyclopedia > Modafinil
Modafinil
Systematic (IUPAC) name
2-benzhydrylsulfinylethanamide
Identifiers
CAS number 68693-11-8
ATC code N06BA07
PubChem 4236
DrugBank APRD00534
Chemical data
Formula C15H15NO2S 
Mol. mass 273.351 g/mol
Pharmacokinetic data
Bioavailability not known as yet
Protein binding 60%
Metabolism Hepatic, including CYP3A4 and other pathways
Half life 8-18 hours
Excretion Urine (as metabolites)
Therapeutic considerations
Pregnancy cat.

C Image File history File links Modafinil. ... Image File history File links No higher resolution available. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System containing Psychoanaleptics. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... This article or section does not cite any references or sources. ... General Name, symbol, number carbon, C, 6 Chemical series nonmetals Group, period, block 14, 2, p Appearance black (graphite) colorless (diamond) Standard atomic weight 12. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... General Name, Symbol, Number sulfur, S, 16 Chemical series nonmetals Group, Period, Block 16, 3, p Appearance lemon yellow Standard atomic weight 32. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... A drugs efficacy may be affected by the degree to which it binds to the proteins within blood plasma. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... Cytochrome P450 3A4 (abbreviated CYP3A4) (EC 1. ... It has been suggested that Effective half-life be merged into this article or section. ... Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ...

Legal status

Schedule IV (US), POM (UK) The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ...

Routes Oral

Modafinil is a eugeroic drug generally prescribed to treat narcolepsy, made by the pharmaceutical company Cephalon Inc. It is not a typical stimulant and is often described as a "wakefulness promoting agent." The drug is sometimes prescribed off-label for ADD/ADHD. In mass-media advertisements and websites, Cephalon markets the drug for improving 'alertness' and reducing 'excessive daytime sleepiness.' In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Eugeroics are a class of stimulants that produce long-lasting mental arousal. ... Narcolepsy is a neurological condition most characterized by Excessive Daytime Sleepiness (EDS). ... The cephalon is the foremost portion of the segmented body of a trilobite. ... Stimulants are drugs that temporarily increase alertness and wakefulness. ... DISCLAIMER Please remember that Wikipedia is offered for informational use only. ...

Contents

Commercial trade names

  • Provigil (U.S., UK, Italy, Belgium)
  • Vigil (Germany)
  • Modalert, Provake, Modapro (India)
  • Modiodal (France, Mexico, Turkey, Greece, Sweden, Denmark)
  • Modavigil (Australia)
  • Alertec (Canada)
  • Vigicer (Argentina)
  • Resotyl, Mentix, Alertex (Chile)
  • Modasomil (Switzerland)

Indications

In the United States, Modafinil is approved by FDA 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). The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... Narcolepsy is a neurological condition most characterized by Excessive Daytime Sleepiness (EDS). ... Sleep apnea or sleep apnoea is a sleep disorder characterized by pauses in breathing during sleep. ... Hypopnœa is a medical term for abnormally shallow breathing or slow respiratory rate. ... Shift work sleep disorder affects people who frequently experience jet lag, either from travel, or by shifting their work or sleep schedules frequently. ... Idiopathic means arising spontaneously or from an obscure or unknown cause. ... Hypersomnia, also known as excessive daytime sleepiness (EDS), is excessive amount of sleepiness. ...


A single dose of 200 mg taken shortly after waking is the usual initial dosage, which may be increased up to 400 mg per day if necessary. Some patients will need to divide their total dose over two or more smaller doses in order to maintain effectiveness throughout the day and/or to reduce the incidence of side-effects. In patients with cirrhosis of the liver or severely compromised renal function, these figures should be halved. The kilogram or kilogramme (symbol: kg) is the SI base unit of mass. ... The kilogram or kilogramme (symbol: kg) is the SI base unit of mass. ... Cirrhosis of the liver is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... The liver is an organ present in vertebrates and some other animals. ...


Cephalon plans to conduct clinical trials evaluating the use of the new longer-lasting Nuvigil (R-modafinil) as a "truly once-a-day" medication for serious conditions such as bipolar depression, cognition associated with schizophrenia, and excessive sleepiness and fatigue in conditions such as Parkinson's disease and cancer. Nuvigil contains armodafinil which is a single-isomer formulation of modafinil. It has a longer half-life than modafinil and therefore would need to be taken less often.[1] Armodafinil (Nuvigil®) is an eugeroic drug produced by the pharmaceutical company Cephalon Inc. ...


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, in treating ADHD, and as an adjunct to antidepressants (particularly in individuals with significant residual fatigue). It has a positive profile for depression because in addition to reducing fatigue, it increases subjective mood and friendliness.[2] Attention-Deficit/Hyperactivity Disorder (ADHD) previously known as Attention Deficit Disorder (ADD), is generally considered to be a developmental disorder, largely neurological in nature, affecting about 5% of the worlds population. ...


Suppress need for sleep

In suppressing the need for sleep, it is generally administered 1-3 times daily in doses of 100-200 mg, up to 600 mg/day. Users without prior experience with stimulants generally respond well to lower doses.


Smart drug

Yet another off-label use for modafinil is as a nootropic, or a "smart drug." It has been demonstrated to have cognitive enhancing[2][3] effects when taken by healthy non-sleep-deprived users in doses of 100-400 mg once a day. There is also evidence that it has neuroprotective[4] effects. Nootropics, popularly referred to as smart drugs and smart nutrients, are substances which boost human cognitive abilities (the functions and capacities of the brain). ... Serving to protect neurons from injury or degeneration. ...


Doping agent

Modafinil has received some publicity in the past when several athletes were discovered allegedly using it as a 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 positive impact on an athlete's performance. However, anectdotal evidence indicates that Modafinil does indeed enhance physical performance. This article needs additional references or sources for verification. ...


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 100-200 mg at the start of days self-assessed as being potentially excessively fatiguing. In 2000, the manufacturer, 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 effective.[5]


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). Some studies have shown the use of modafinil in the treatment of ADHD is associated with significant improvements in primary outcome measures. Cognitive function in ADHD patients may also improve following modafinil treatment, in some studies. Studies for ADHD report insomnia and headache were the most common adverse effects, seen in approximately 20% of treated individuals. 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.[6]


In December of 2004, Cephalon submitted a supplemental new drug application (sNDA) to market Sparlon, a brand name of tablets containing higher doses of modafinil (85, 170, 255, 340, and 425 mg) 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 1,000 patient trial, including one which was thought to be likely a case of Stevens-Johnson syndrome.[7][8] 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. Stevens-Johnson syndrome (SJS) is a severe and life-threatening condition. ...


Modafinil is contraindicated for patients with a history of cardiac events. However, one 2005 case report [9] positively describes transitioning a 78 year old with "significant cardiac comorbidity" from Methylphenidate (5mg b.i.d. ) to Modanafil 200mg daily. For an adult, 10mg of Methylphenidate daily is not an effective ADHD monotherapy[citation needed], while 200mg is the Modanafil maintenance baseline.[citation needed] Thus, Modanafil's physiologic (and political) advantages over conventional ADHD therapies should not be dismissed out of hand, but rather discussed individually with a physician/neurologist or psychiatrist. This page is about the muscular organ, the Heart. ... In medicine and in psychiatry, comorbidity is either The presence of one or more disorders (or diseases) in addition to a primary disease or disorder; or The effect of such additional disorders or diseases. ... Vitamin R redirects here. ... This is a list of medical acronyms and abbreviations. ... Vitamin R redirects here. ... Physiology (in Greek physis = nature and logos = word) is the study of the mechanical, physical, and biochemical functions of living organisms. ... There are several clinically proven effective options available to treat people diagnosed with attention-deficit hyperactivity disorder (ADHD). ... The Doctor by Luke Fildes This article is about the term physician, one type of doctor; for other uses of the word doctor see Doctor. ... Neurology is the branch of medicine that deals with the nervous system and disorders affecting it. ... Psychiatry is a branch of medicine that studies and treats mental and emotional disorders (see mental illness). ...


Other uses

Modafinil is also used off-label to treat sedation and fatigue in depression[10][11], myotonic dystrophy[12], opioid induced sleepiness[13], spastic cerebral palsy[14], and Parkinson’s disease[15]. It increases subjective mood and friendliness. [2]


Experimental uses

Cocaine/amphetamine addiction

In January 2005, researchers at the University of Pennsylvania published the results of a small study, which found that modafinil may help recovering cocaine addicts fight their addiction. Similar published case reports suggest that modafinil might also be useful in the treatment of amphetamine addiction. This article is about the private Ivy League university in Philadelphia. ... Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. ... Look up addiction in Wiktionary, the free dictionary. ... Amphetamine or Amfetamine (Alpha-Methyl-PHenEThylAMINE), also known as, beta-phenyl-isopropylamine, and benzedrine, is a prescription stimulant commonly used to treat Attention-deficit hyperactivity disorder (ADHD) in adults and children. ...


Weight loss

Studies on modafinil (even those on healthy weight individuals) indicate that it has an appetite reducing/weight loss effect.[16][2][17][18][19]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.


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.[20]


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.[16]


Conversely, a U.S. patent (#6,455,588) on using modafinil as an appetite stimulating agent has been filed by Cephalon in 2000.


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.[21] The Epworth Sleepiness Scale is a questionnaire intended to measure daytime sleepiness. ...


Contraindications and warnings

It is important to consult with your physician before using Modafinil, particularly for those with: The Doctor by Luke Fildes This article is about the term physician, one type of doctor; for other uses of the word doctor see Doctor. ...

  • Hypersensitivity to the drug or other constituents of the tablets, or
  • Previous cardiovascular problems, particularly while using other stimulants, or
  • Cardiac conditions, particularly:

See the ADHD section for discussion of transitions to Modafinil from high dose stimulant regimens. Left ventricular hypertrophy (LVH) is the abnormal thickening of the myocardium (muscle) of the left ventricle of the heart. ... Mitral valve prolapse (MVP) is a heart valve condition marked by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. ... In medicine, a disease is asymptomatic when it is at a stage where the patient does not experience symptoms. ...


MAOIs conflict with a very broad range of substances. Modafinil has not been tested with MAOIs, but is expected to significantly potentiate the drug response (factor of 4 or more). Using Modafinil within two weeks of an MAOI, such as Parnate (tranylcypromine), Nardil (phenelzine), Emsam (deprenyl), or Marplan (isocarboxazid) creates the potential for hazardous and potentially fatal side-effects. Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs prescribed for the treatment of depression. ... Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs prescribed for the treatment of depression. ... Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs prescribed for the treatment of depression. ... Tranylcypromine (sold under the brand name Parnate®) is a monoamine oxidase inhibitor (MAOI) used as an antidepressant drug. ... Phenelzine (brand name Nardil) is an antidepressant drug that belongs to the monoamine oxidase inhibitor (MAOI) class of drugs. ... Selegiline/l-Deprenyl Selegiline (l-deprenyl, Eldepryl® or Anipryl® [veterinary]) is a drug used for the treatment of early-stage Parkinsons disease and senile dementia. ... Isocarboxazid is a nonselective hydrazine-derived monoamine oxidase inhibitor used in treatment resistant depression. ...


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. This article includes a list of works cited or a list of external links, but its sources remain unclear because it lacks in-text citations. ... An anxiolytic is a drug prescribed for the treatment of symptoms of anxiety. ...


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.

  • Alcohol and similar depressants should be avoided if at all possible while taking Modafinil.

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: “Placebo effect” redirects here. ...

Additionally, gastrointestinal distress, which may be alleviated by taking the drug after a meal, aggressiveness and skin irritation have been reported, but are rare. A headache (cephalalgia in medical terminology) is a condition of pain in the head; sometimes neck or upper back pain may also be interpreted as a headache. ... For the Beck song, see Nausea (song). ... Anxiety is a complex combination of the feeling of fear, apprehension and worry often accompanied by physical sensations such as palpitations, chest pain and/or shortness of breath. ... This article is about the sleeping disorder. ... This article includes a list of works cited or a list of external links, but its sources remain unclear because it lacks in-text citations. ... Anorexia (deriving from the Greek α(ν)- (a(n)-, a prefix that denotes absence) + όρεξη (orexe) = appetite) is the decreased sensation of appetite. ... Xerostomia is the medical term for a dry mouth due to a lack of saliva. ... In medicine, chest pain is a symptom of a number of conditions and is generally considered a medical emergency, unless the patient is a known angina pectoris sufferer and the symptoms are familiar (appearing at exertion and resolving at rest, known as stable angina). When the chest pain is not... This article does not cite any references or sources. ... This article or section does not cite any references or sources. ... The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... // Pre-syncope is a sensation of feeling faint. ... Paresthesia or paraesthesia (in British English) is a sensation of tingling, pricking, or numbness of a persons skin with no apparent long-term physical effect, more generally known as the feeling of pins and needles or of a limb being asleep (but not directly related to the phenomenon of... Pharyngitis (far-in-jī tis) is a painful inflammation of the pharynx, and is colloquially referred to as a sore throat. ... For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and...


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.[22]


Modafinil may have an adverse effect on hormonal contraceptives, lasting for a month after cessation of dosage.[23] Hormonal contraception refers to birth control methods that act on the hormonal system. ...


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).[24] Consequently, oral LD50 of modafinil in humans is not known exactly. However, it appears to be higher than oral LD50 of caffeine. An LD50 test being administered In toxicology, the LD50 or colloquially semilethal dose of a particular substance is a measure of how much constitutes a lethal dose. ... Caffeine is a xanthine alkaloid compound that acts as a stimulant in humans. ... Caffeine is a xanthine alkaloid compound that acts as a stimulant in humans. ...


Military use

Militaries of several countries are known to have expressed interest in Modafinil as an alternative for amphetamine - the drug traditionally employed in sleep-deprivation situations. Amphetamine or Amfetamine (Alpha-Methyl-PHenEThylAMINE), also known as, beta-phenyl-isopropylamine, and benzedrine, is a prescription stimulant commonly used to treat Attention-deficit hyperactivity disorder (ADHD) in adults and children. ...


The French government indicated that the Foreign Legion used modafinil during certain covert operations. The UK's Ministry of Defence has admitted conducting ongoing research into Modafinil.[25] In the United States military, Modafinil has been approved for use on certain Air Force missions, and it is being investigated for other uses.[26]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.[27]However, significant levels of nausea and vertigo were observed. Another study of fighter pilots showed that 300 mg 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.[28] 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.[29] “Legionnaire” redirects here. ... The Ministry of Defence (MOD) is the United Kingdom government department responsible for implementation of government defence policy and the headquarters of the British Armed Forces. ... The United States Air Forces F-117A Nighthawk is the worlds first operational aircraft designed to exploit low-observable stealth technology. ...


Pharmacology

The exact mechanism of action is unclear, although in vitro studies have shown it to inhibit the reuptake of dopamine and, more potently, norepinephrine. 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. Wikipedia does not yet have an article with this exact name. ... Wiktionary has a definition of: In vitro In vitro (Latin: within glass) means within a test tube, or, more generally, outside a living organism or cell. ... Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by the neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse. ... Dopamine is a phenethylamine naturally produced by the human body. ... Norepinephrine (INN)(abbr. ... Antagonists In medicine and biology, a receptor antagonist is a ligand that inhibits the function of an agonist and inverse agonist for a specific receptor. ... Amphetamine or Amfetamine (Alpha-Methyl-PHenEThylAMINE), also known as, beta-phenyl-isopropylamine, and benzedrine, is a prescription stimulant commonly used to treat Attention-deficit hyperactivity disorder (ADHD) in adults and children. ... Glutamate is the anion of glutamic acid. ... Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model... Euphoria is a medically recognized emotional state related to happiness. ...


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. Dose can refer to: Dose (album), an album by the jam band Govt Mule Dose (song), a song by the band Filter Dose (magazine), a free daily Canadian magazine In medicine: Effective dose, the smallest amount of a substance required to produce a measurable effect on a living organism... Chlorination is the process of adding the element chlorine to water as a method of water purification to make it fit for human consumption as drinking water. ... Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. ... Norepinephrine (INN)(abbr. ... Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. ... The ventrolateral preoptic nucleus (VLPO) is a group of neurons that seem to be active during sleep. ...


Modafinil has a binding coefficient (Ki) of about 4,000 nmol/L for the dopamine reuptake transporter, and in excess of 10,000 nmol/L for the norepinephrine reuptake transporter. The mole (symbol: mol) is the SI base unit that measures an amount of substance. ... The liter (spelled liter in American English and litre in Commonwealth English) is a unit of volume. ...


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. Peptides are the family of molecules formed from the linking, in a defined order, of various amino acids. ... Orexins, also called hypocretins, are the common names given to a pair of highly excititory neuropeptide hormones that were simultaneously discovered by two groups of reseachers in rat brains. ... Orexins, also called hypocretins, are the common names given to a pair of highly excititory neuropeptide hormones that were simultaneously discovered by two groups of reseachers in rat brains. ... The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). ... Norepinephrine (INN)(abbr. ... This article or section does not cite any references or sources. ...


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.[30] This article or section does not cite any references or sources. ...


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 3 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.[21]


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. Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... This page is a candidate for speedy deletion. ... CYP2B6 is a member of the Cytochrome P450 group of enzymes. ... Cytochrome P450 3A4 (abbreviated CYP3A4) (EC 1. ... Cytochrome P450 2C9 (abbreviated CYP2C9), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. ... Cytochrome P450 2C19 (abbreviated CYP2C19), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. ... P-glycoproteins are a type of protein that appear to have developed as a mechanism to protect the body from harmful substances by acting as efflux transporters. ... Digoxin (INN) (IPA: ) is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata. ...


Cmax 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. area under the curve: AUC means area under the curve. This is the area under the concentration time curve. ...


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.[31] Adrafinil chemical structure Adrafinil is a mild central nervous system stimulant drug used to relieve excessive sleepiness and inattention in elderly patients. ...


Formulation patent

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 granting of the orphan drug status is designed to encourage the development of drugs which are necessary but would be prohibitively expensive/un-profitable to develop under normal circumstances. ... is the 89th day of the year (90th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday (link displays full 2006 calendar) of the Gregorian calendar. ...


Particle size patent

Cephalon filed for 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.[32] However, a settlement in which Cephalon apparently paid out US$ 200 million to four generic drug manufacturers[33] may mean that generic forms of the drug will become available in April 2012 (October 2011 prior to the six month extension). is the 96th day of the year (97th in leap years) in the Gregorian calendar. ... 2015 (MMXV) will be a common year starting on Thursday of the Gregorian calendar. ...


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.


Other Wakefullness Promoting Agents

Up to now, modafinil, has been a unique drug without competition. However in 2007, Vanda Pharmaceuticals, Inc. began Phase II clinical trials for VSF-173, a medicine also targeted for excessive sleepiness.[34]


Price

Brand-name Provigil is very expensive. Currently it retails in the United States for $7-8 per one 200 mg pill.[35] Modiodal and Alertec are somewhat cheaper. Modalert, the version of Modafinil produced by an Indian company Sun Pharma, is the most affordable and can be found as cheaply as $1-2 per one 200 mg pill. [36] Within India, Modalert can be found even cheaper at the rate of 6-7rs. per 100mg pill ($0.15-$0.17 at the time of this writing).


As of January 2007, no generic versions of Provigil exist yet; prices can be expected to go down considerably if Cephalon's monopoly in the U.S. market is successfully challenged.


Not all U.S. health insurance companies cover Modafinil/Provigil, and those that do may require proof of severity of one's condition before paying for the drug. As a result, many Americans in need of this medication turn towards online pharmacies or try to bring Modafinil from neighboring countries (Canada and Mexico). One is advised to examine the following section before attempting to buy Modafinil.


Legal status

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 is related to already banned substances, so the decisions stand. The agency added modafinil to the list of prohibited substances on August 3, 2004, ten days before the start of the 2004 Summer Olympics. The World Anti-Doping Agency (WADA) is an independent foundation created through a collective initiative led by the International Olympic Committee (IOC). ... is the 215th day of the year (216th in leap years) in the Gregorian calendar. ... Year 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ... The ceremony for the lighting of the flame is arranged as a pagan pageant, with priestesses dancing. ...


Modafinil is currently 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 ( and, therefore, to buy from most online pharmacies ), with or without a prescription.[37] It is also illegal to possess without a valid prescription. 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.[38] 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. 2005 is a common year starting on Saturday of the Gregorian calendar. ... The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... Since 1973, the DEA has enforced the drug laws in the United States. ... Recently, a number of pharmacies have begun operating over the internet. ... Adrafinil chemical structure Adrafinil is a mild central nervous system stimulant drug used to relieve excessive sleepiness and inattention in elderly patients. ...


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

The Controlled Drugs and Substances Act is Canadas federal drug control statute. ... The Canada Border Services Agency (CBSA) (French: Agence des services frontaliers du Canada - ASFC) is responsible for Canadas border operations. ... The Misuse of Drugs Act 1971 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs and drug-like substances, as listed under the Act, and to enable international co-operation against illegal drug trafficking. ... A medical prescription ) is an order (often in written form) by a qualified health care professional to a pharmacist or other therapist for a treatment to be provided to their patient. ...

In Popular Culture

In the film The Invasion, Nicole Kidman is seen rummaging in a pharmacy for some wakefullness promoting agents. She grabs a bottle of "modifinil" 1 gram dosage. The common dosages for modafinil are 100 mg, 200 mg. The premise of the movie is the the alien virus works its evil during sleep so she needs to stay awake until she finds a cure. The Invasion, previously known as Invasion and The Visiting, is a 2007 science fiction film based on a screenplay by Dave Kajganich, originally meant to be based on the 1956 film Invasion of the Body Snatchers. ... Nicole Mary Kidman AC (born June 20, 1967), is an Australian[1] Academy Award winning actress. ...


See also

Adrafinil chemical structure Adrafinil is a mild central nervous system stimulant drug used to relieve excessive sleepiness and inattention in elderly patients. ... Armodafinil (Nuvigil®) is a drug produced by the pharmaceutical company Cephalon, currently in the process of receiving FDA approval. ... Human reliability is related to the field of human factors engineering, and refers to the reliability of humans in fields such as manufacturing, transportation, the military, or medicine. ... Hypopnœa is a medical term for abnormally shallow breathing or slow respiratory rate. ... Narcolepsy is a neurological condition most characterized by Excessive Daytime Sleepiness (EDS). ... Seasonal affective disorder, or SAD, also known as winter depression or winter blues is an affective, or mood, disorder. ... Shift work sleep disorder affects people who frequently experience jet lag, either from travel, or by shifting their work or sleep schedules frequently. ... Sleep apnea or sleep apnoea is a sleep disorder characterized by pauses in breathing during sleep. ... Nootropics are so-called smart drugs. ...

References

  1. ^ Cephalon Provides Update Related to NUVIGIL(TM) New Drug Application. Cephalon.com (2007-03-30). Retrieved on 2007-07-21.
  2. ^ a b c d Hart, Carl (2006), "Modafinil attenuates disruptions in cognitive performance during simulated night-shift work.", Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 31 (7): 1526-1536
  3. ^ Turner, Danielle (January 2003), "Cognitive enhancing effects of modafinil in healthy volunteers", Psychopharmacology 165 (3): 260-269
  4. ^ Jenner, P (July 2000), "Antiparkinsonian and neuroprotective effects of modafinil in the mptp-treated common marmoset", Experimental Brain Research 133 (2): 178-188
  5. ^ Rammohan, K W (2002), "Efficacy and safety of modafinil (Provigil®) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study", Journal of Neurology Neurosurgery and Psychiatry 72 (2): 179-183
  6. ^ Lindsay, SE; Gudelsky GA, Heaton PC (October 2006). "Use of modafinil for the treatment of attention deficit/hyperactivity disorder". The Annals of Pharmacotherapy 40 (10). Retrieved on 2006-12-07. 
  7. ^ Psychopharmacologic Drugs Advisory Committee (transcript). FDA (2006-03-23).
  8. ^ Modafinil (CEP-1538) Tablets Supplemental NDA 20-717/S-019 ADHD Indication Briefing Document for Psychopharmacologic Drugs Advisory Committee Meeting (PDF). FDA (2006-03-23). Retrieved on 2007-07-21.
  9. ^ Xiong, M.D., Glen L.; Eric J. Christopher, M.D., and Jason Goebel, M.D.. "Modafinil as an Alternative to Methylphenidate as Augmentation for Depression Treatment". Psychosomatics 46: 578-579. DOI:10.1176/appi.psy.46.6.578. “Case report: Modafinil 200mg daily replacing Methylphenidate 5mg b.i.d in 78 year old cardiac patient” 
  10. ^ Menza, MA (2000), "Modafinil augmentation of antidepressant treatment in depression", J Clin Psychiatry 61 (11): 378-381
  11. ^ DeBattista, C (2004), "A prospective trial of modafinil as an adjunctive treatment of major depression", J Clin Psychopharmacol 24 (1): 87-90
  12. ^ MacDonald, JR (2002), "Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy", Neurology 59: 1876-1880
  13. ^ Webster, L (June 2003), "Modafinil treatment of opioid-induced sedation", Pain Med 4 (2): 135-140
  14. ^ Hurst, DL (March 2002), "Use of modafinil in cerebral palsy", J Child Neurology 17 (3): 169-172
  15. ^ Nieves, AV (March 2002), "Treatment of excessive daytime sleepiness in patients with Parkinson’s disease with modafinil", Clin. Neuropharmacol. 25 (2): 111-114
  16. ^ a b Henderson, David (April-June 2005), "Modafinil-Associated Weight Loss in a Clozapine-Treated Schizoaffective Disorder Patient", Annals of Clinical Psychiatry; 17 (2): 95-97
  17. ^ Efficacy and Safety of Modafinil Film-Coated Tablets in Children and Adolescents
  18. ^ Vaishnavi, Sandeep (2006), "Modafinil for atypical depression: effects of open-label and double-blind discontinuation treatment.", Journal of clinical psychopharmacology 26 (4): 373-378
  19. ^ Michael, Thase (2006), "Modafinil augmentation of SSRI therapy in patients with major depressive disorder and excessive sleepiness and fatigue: a 12-week, open-label extension study", CNS Spectrums 11 (2): 93-101
  20. ^ Makris, Angela (April 2004), "Wake-promoting agents with different mechanisms of action: comparison of effects of modafinil and amphetamine on food intake and cardiovascular activity", Appetite 42 (2): 185
  21. ^ a b Bonaventure, P., Letavic, M., Dugovich, C., Wilson, S., Alusio, L., Pudiak, C., et al. (2007, April 15). Histamine H(3) receptor antagonists: From target identification to drug leads. Biochemical Pharmocology, 73(2007 Apr 15; Vol. 73 (8), pp. 1084-96), 1084-96. Abstract retrieved April 2, 2007, from Medline database.
  22. ^ Oskooilar, Nader (October 2005). "A Case of Premature Ventricular Contractions With Modafinil". American Journal of Psychiatry 162: 1983-a-1984. DOI:10.1176/appi.ajp.162.10.1983-a. 
  23. ^ MedlinePlus Drug Information: Modafinil. NIH (2005-07-01). Retrieved on 2007-07-21.
  24. ^ FDA Approved Labeling Text for Provigil (PDF). FDA (2004-01-23).
  25. ^ BBC report on MoD research into Modafinil
  26. ^ Modafinil and Management of Aircrew Fatigue - United States Air Force memo
  27. ^ The Effects of Modafinil on Aviator Performance During 40 Hours of Continuous Wakefulness
  28. ^ The efficacy of Modafinil for sustaining alertness and simulator flight performance in F-117 pilots during 37 hours of continuous wakefulness
  29. ^ http://stinet.dtic.mil/cgi-bin/GetTRDoc?AD=ADA454558&Location=U2&doc=GetTRDoc.pdf A Double-Blind Placebo-Controlled Investigation of the Efficacy of Modafinil for Maintaining Alertness and Performance in Sustained Military Ground Operations
  30. ^ Ishizuka, T; Sakamoto Y, Sakurai T, Yamatodani A (2003). "Modafinil increases histamine release in the anterior hypothalamus of rats". Neuroscience Letters 339 (2): 143-6. PMID 12614915. 
  31. ^ Dockets Entered On December 26, 2006. FDA (2006-12-26). Retrieved on 2007-07-21. “2005P-0265 Over-the Counter Sale of Modafinil”
  32. ^ "Cephalon gets six-month Provigil patent extension", Philadelphia Business Journal, 2006-03-28. Retrieved on 2007-07-21. 
  33. ^ Pringle, Evelyn (2006-03-20). Sparlon: Just What Kids Need - Another ADHD Drug. Retrieved on 2007-07-21.
  34. ^ www.vandapharma.com/development.html.
  35. ^ ALL PRICES FOR: Provigil - Brand Version : 200 mg. PharmacyChecker.com. Retrieved on 2007-07-21.
  36. ^ MODALERT.
  37. ^ Is It Illegal to Obtain Controlled Substances From the Internet?. United States Drug Enforcement Administration. Retrieved on 2007-07-21.
  38. ^ USC 201 Section 1301.26 Exemptions from import or export requirements for personal medical use. United States Department of Justice (1997-03-24).
  39. ^ (2006-10-04) "Regulations Amending the Food and Drug Regulations (1184 — Modafinil)". Canada Gazette 140 (20). 
  40. ^ Estupefacientes y Psicotrópicos (Spanish). Comisión Federal para la Protección contra Riesgos Sanitarios. Retrieved on 2007-07-21.
  41. ^ Purchasing Modafinil in the UK. modanifil-source.co.uk (2007-07-15). Retrieved on 2007-07-21.

Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday (link displays full 2006 calendar) of the Gregorian calendar. ... is the 341st day of the year (342nd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... kkdkd ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... National Institutes of Health Building 50 at NIH Clinical Center - Building 10 The National Institutes of Health (NIH) is an agency of the United States Department of Health and Human Services and is the primary agency of the United States government responsible for biomedical research. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ... The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ... The DEAs enforcement activities may take agents anywhere from distant countries to suburban U.S. homes. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ... DOJ headquarters in Washington, D.C. Justice Department redirects here. ... The Canada Gazette is an official publication by the government of Canada that publishes all laws and Orders in Council issued by the government. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 202nd day of the year (203rd in leap years) in the Gregorian calendar. ...

External links

  • Provigil corporate website
  • Cephalon corporate website
  • Cephalon's guerrilla marketing website for Provigil - does not mention medication or the product name
  • Modafinil information from BLTC Research, an advocate of psychopharmacology
  • Page about modafinil at Erowid
  • Information on modafinil use from independent source
  • "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
  • Information on modafinil and histamine release from NIH
  • Felleskatalogen Norwegian language SPC database
  • Sleep Research Online 1(1): 49-61, 1998 Paper on wake-promoting effects of stimulants
  • RxList Patient Information for modafinil users
  • | "How to stay up all day if you've been up all night " Helium article, personal experience, 2007, Helium Ecosystem
  • Modafinil Articles

  Results from FactBites:
 
Modafinil - Wikipedia, the free encyclopedia (1605 words)
Modafinil blocks the reuptake of norepinephrine by the noradrenergic terminals on sleep-promoting neurons from the ventrolateral preoptic nucleus (VLPO).
Modafinil is currently classified as a Schedule IV controlled substance under United States federal law.
"Modafinil increases histamine release in the anterior hypothalamus of rats.".
  More results at FactBites »

 
 

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