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Modafinil

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Post Uploaded Date : September 11, 2023 Last Updated Date : September 13, 2024
modafinil-chemical-structure

What is Modafinil and How Does it Work?

What is Modafinil?

Modafinil is a non-amphetamine Central Nervous System (CNS) stimulant that enhances the mental and physical activity of the brain. This drug class improves productivity, endurance, wakefulness, and alertness by altering chemical signals carrying messages in the CNS.

It was initially developed by Michel Jouvet, a French neuroscientist, in the 1970s in association with the Lafon Laboratories, a pioneer in developing and marketing Central Nervous System medications.

Modafinil was approved by the Food and Drug Administration (FDA) in the United States in 1998 for treating Excessive Daytime Sleepiness in association with Narcolepsy. Currently, it has emerged as the 302nd most commonly prescribed medication in the country.

Modafinil Classification

Modafinil is classified as a Schedule IV controlled substance, according to the Controlled Substances Act (CSA) by the Drug Enforcement Administration (DEA) in the United States.

It is a drug category with approved medical use and a low risk of abuse and dependency.

Modafinil, like all Schedule IV medication, is obtained through medical prescription and is unavailable over the counter. However, buying Modafinil without a prescription from a licensed online pharmacy is legal.

How Does Modafinil Work

Modafinil’s wake-promoting mechanism of action includes its effect on increasing the secretion of Histamine (HA), Norepinephrine (NE), Serotonin (5-HT), Orexin, and Dopamine (DA) in the brain.

The nerve cells release the Histamine, Serotonin, and Norepinephrine neurotransmitters associated with regulating the sleep-wake cycle, resulting in alertness and arousal in Narcoleptic patients.

Orexin is a protein synthesized by the neurons and is responsible for maintaining vigilance.

Dopamine Reuptake Inhibitor

Mignot et al. (1994) suggest that Modafinil inhibits dopamine reuptake by binding to the dopamine reuptake pump, thus increasing its concentration in the body. This increased extracellular dopamine in the brain improves energy, wakefulness, alertness, stamina, and focus. The cognitive-enhancing property of Modafinil enables it to enhance memory through the secretion of serotonin, norepinephrine, and glutamate.

Half-life Of Modafinil

The half-life of Modafinil is between 12 and 15 hours and represents the time taken by the body to reduce the drug's active substance to half. It is a crucial parameter in understanding how long Modafinil remains effective and how often it needs to be administered. The effect of Modafinil lasts for 10 to 12 hours, but in a few cases, it may last as long as 15 hours.

Pharmacokinetics of Modafinil

The pharmacokinetics of Modafinil deal with the movement of the medication in the body, including its metabolism and excretion. After oral administration, the Modafinil tablet is metabolized in the liver to form Modafinil Sulfone (CRL-41056) and Modafinil acid (CRL-40467). These metabolites are an end product of metabolism and do not contribute to Modafinil's cognitive or wakefulness-promoting effect. The metabolites of Modafinil are excreted through the kidneys as urine.

Absorption Easily absorbed after oral administration
Metabolism Hepatic metabolism via multiple pathways.
Excretion Urine in the form of urine (80%).

Chemical Properties Of Modafinil

The chemical name of Modafinil is 2-[(phenylmethyl)sulfinyl] acetamide. It is a sulfoxide where the two hydrogen molecules attached to one methyl group are replaced with the phenyl group, and the other hydrogen attached to the methyl group is replaced by the carbamoyl (aminocarbonyl) group.

C15H15NO2S

chemical-properties-of-modafinil
  • C15

    Pentadecylic acid

  • H15

    N-[(1R,3R)-3-hydroxy-1-(hydroxymethyl)-3-phenylpropyl]pentadecanamide

  • NO2

    Nitrogen Dioxide

  • S

    Sulfur

The molecular formula of Modafinil is C15H15NO2S, and its molecular weight is 273.35 g/mol. It is sparingly or slightly soluble in acetone and methanol.

List of Ingredients

Modafinil tablets comprise lactose monohydrate, pregelatinized starch, croscarmellose sodium, lactose monohydrate, povidone, microcrystalline cellulose, and magnesium stearate as inactive compounds.

Modafinil Brand Name

Modafinil is a chemical compound (C15H15NO2S) that serves as an active compound in generic tablets and brand medications.

Generic Modafinil tablets are formulated with the same active compound (Modafinil salt) and are labeled and marketed by the compound name itself.

On the other hand, Modalert and Modvigil are brand drugs, which means they contain Modafinil salt as their active compound but are manufactured and marketed under different names given by specific pharmaceutical companies.

Modafinil Brand Name Pharmaceutical Company
Modalert Sun Pharmaceutical Industries Ltd.
Modvigil Hab Pharmaceuticals and Research Ltd.
Provigil Teva Pharmaceuticals.

It is also available under numerous other brand names, including Alertec, Movigil, Stavigile, Vigimax, Zalux, and Modafinilo.

Modafinil Pill Identifier

Modalert and Modvigil are both white round tablets that are 9mm (0.9cm) in size. It is imprinted with "MOD 200" and "APO." However, the tablet may look different depending on the Modafinil brand and its manufacturing company.

Uses Of Modafinil- Why Is This Medication Prescribed?

Uses Of Modafinil

The medical use of Modafinil is approved for the treatment of Excessive daytime sleepiness associated with Obstructive Sleep Apnea, Shift Work Sleep Disorder, and Narcolepsy. It is, however, not a treatment option for its underlying condition, such as sudden muscle loss, also known as cataplexy.

Modafinil is prescribed along with other breathing devices or treatment options to prevent excessive sleepiness caused by obstructive sleep apnea/hypopnea syndrome (OSAHS). It is a condition that is characterized by brief shallow breathing episodes throughout the night, resulting in restless sleep.

Modafinil Off-Label Uses

The most common off-label use of Modafinil is as a cognitive enhancer. A study by Miriam Punzi et al. suggests that Modafinil exerts a significant effect on the cerebellum’s resting activity, which plays a crucial role as a modulator of cognition.

Modafinil’s efficacy in improving Planning and decision-making was indicated by Owen et al. in 1995. It can also enhance cognitive performance in domains such as memory, attention, alertness, executive functions, and response accuracy.

The second common off-label Modafinil includes its ability to significantly improve fatigue in patients with multiple sclerosis and cancer. Dongsoo Kim, in the Journal of Environmental Health and Toxicology, suggests that Modafinil helps patients combat chemotherapy-induced fatigue.

The therapeutic effect of Modafinil on fatigue is modulated by the hypocretin (orexin) system and has shown benefit in improving neurologic disorders such as motor neuron disease and Parkinson’s disease.

Modafinil for ADHD (attention deficit hyperactivity disorder) is not approved by the FDA for medical use but is supported by numerous clinical studies. A 2006 study by Danielle Turner indicates Modafinil has greater efficacy than a placebo in treating ADHD in adults and children. The study suggests that the advantage of Modafinil for ADHD over current therapies is that it can be administered once daily with a lower risk of side effects and abuse.

Benefits Of Modafinil

  • circleThe main advantage of Modafinil over other amphetamine-like stimulants is that it is a well-tolerated drug with a low risk of adverse effects and abuse potency, suggest researchers Michael J. Minzenberg and Cameron S. Carter in a 2007 study.
  • circleA single dose of Modafinil could significantly improve recognition memory, stop-signal reaction time (SSRT), test performance, and visuospatial planning, concludes a study by Turner et al. in 2003.
  • circleTaking Modafinil without consulting a doctor is not advisable for pregnant and lactating women.
  • circleIt has a quick onset of action and starts working within 30 minutes of intake.
  • circleMost healthcare insurance plans cover the cost of this Nootropic.
  • circleModafinil has a lower tendency to cause side effects such as jitteriness, excess locomotor activities, or rebound effects compared to brain stimulants, states Dongsoo Kim in a 2012 study entitled Practical Use and Risk of Modafinil.

Modafinil Dosage Regimens For Maximum Benefits

The starting dose of Modafinil for beginners is 200 mg for all its medically approved uses, including Narcolepsy, obstructive sleep apnea, and shift work sleep disorder.

Renal And Hepatic Dosage Adjustments

No dosage adjustments are required for mild to moderate hepatic (liver) and renal (kidney) impairments. However, the Modafinil dosage should be reduced by half in severe renal and hepatic disorders cases.

Recognizing And Responding To Modafinil Overdosage

The maximum daily dose of Modafinil is 400 mg, and taking a higher dose results in drug overdosing. Modafinil overdose may also arise from coadministering it with other medications and supplements.

A recent study by Rohan Oliver Kandasamy in 2020 suggests that the common findings from the study associated with overdosing on Modafinil include Central nervous system toxicity and tachycardia. Its neurological effects include heightened anxiety, headache, dystonia, agitation, tremors, and dizziness. Apart from the neurological effects, ten other symptoms to recognize Modafinil overdose include

  • circleRestlessness.
  • circleHallucination.
  • circleNervousness.
  • circleChest pain.
  • circleNausea.
  • circleDiarrhea.
  • circleConfusion.
  • circleUncontrollable shaking of a part of the body.
  • circleDifficulty falling asleep or staying asleep.
  • circleFast, slow, or pounding heartbeat.

Responding to a Modafinil overdose should be supportive, focusing on controlling and managing sedation, blood pressure, and dyskinesias. It should be quick and preferably as soon as the symptoms appear.

Missed Doses

If you miss a dose of Modafinil, take it if you remember it before 12 p.m. (Noon) the same day. Skip the missed dose and return to your regular dosing schedule if it is almost bedtime or time for the next dosage. Do not double dose to make up for your missed Modafinil dosage.

Administration Guidelines- How To Take Modafinil?

  • circleModafinil dosage for treating sleep issues with Narcolepsy and Obstructive sleep apnea should be taken in the morning.
  • circleModafinil is an oral pill that should be swallowed with water.
  • circleCrushing, chewing, or breaking the pill is not advisable as it alters Modafinil's absorption rate, resulting in overdosing and reducing the effectiveness of the treatment.
  • circleTake the dose at the same time every day to maximize its benefits. The dosage timing should not be altered without consulting a doctor.
  • circleDo not take large dosages for a longer period of time than prescribed by your doctor, as prolonged use of Modafinil may become habit-forming.
  • circleTake Modafinil with or without food, as it has no effect on the overall Modafinil bioavailability, which determines the extent to which a medication becomes completely available for its intended biological destination. But avoid foods high in fat, as they delay the absorption (tmax) by one hour (60 minutes).
Best Time To Take Modafinil
  • circleAdministering Modafinil tablets before 10 a.m. in the morning is advisable to avoid insomnia.
  • circleFor treating shift work sleep disorder, take Modafinil dosage 1 hour (60 minutes) before starting work.
  • circleFew patients may experience poor control of daytime sleepiness in the afternoon or in the evening. Splitting Modafinil 200 mg dose (100 mg in the morning and 100 mg in the afternoon or evening) will help.

Potential Modafinil Side Effects

Modafinil causes mild to moderate side effects; however, in rare cases, it may result in severe health risks. The following list contains the key common side effects of Modafinil.

Common And Mild Side Effects Of Modafinil Twelve common side effects of Modafinil and their reported cause are listed below.
  • circleDieuretic property of Modafinil causing dehydration- Headache and Dry mouth.
  • circleLong half-life and eugeroic action of Modafinil- Insomnia.
  • circleOverstimulation of the Central Nervous System- Dizziness, Nervousness, Anxiety.
  • circleSlow breakdown of Modafinil by the liver- Diarrhea, Upset Stomach.
  • circleHigh level of neurotransmitters
    • circleSecretion of Dopamine and Histamine causes loss of appetite.
    • circleSecretion of Dopamine and Serotonin triggers nausea by the stimulation of the chemoreceptor trigger zone (CTZ) of the brain.
  • circleAllergic reaction (due to histamine secretion by Modafinil)- Runny Nose.
  • circleDrug Interaction or previous medical history- Chest Pain.

3 Serious And Rare Modafinil Side Effects

The serious side effects of Modafinil are not common and occur in rare instances. Inform your doctor and get medical assistance immediately if you experience any of the below-mentioned side effects.

Severe rash

Within the first week of Modafinil administration, severe rash may develop along with fever and vomiting. It may also affect the heart, liver, kidneys, and lungs. Two other notable allergic reactions that require immediate medical help include trouble swallowing or breathing and swelling of the face, tongue, and lips.

Cardiac Disorder

Modafinil can affect the heart, causing palpitation (pounding of the heart), tachycardia (heart rate over 100 beats per minute at rest), and high blood pressure. It is more common in people with a history of heart condition or hypertension.

Mental Health Effects

Modafinil can cause irritability, depression, and Confusion in rare cases. A few individuals with previous mental health issues may also experience suicidal thoughts and symptoms of psychosis, including aggression, delusions, mania, and hallucinations.

Long-Term Side Effects Of Modafinil
  • circleLong-term use of Modafinil increases the risk of developing physical and psychological dependence.
  • circleSuch patients are more likely to experience insomnia as prolonged Modafinil use disturbs the sleep architecture.

Modafinil Safety Advice - Things That One Should Know

  • circleModafinil causes lightheadedness, dizziness, and drowsiness; thus, using heavy machinery or driving can be dangerous.
  • circleIt should not be taken during pregnancy because of the increased risk of congenital malformations in the fetus.
  • circleDue to the low molecular weight of Modafinil (273.35 g/mol), it can cross over to breast milk and be available for 15 hours, says Sanjay Aurora in a 2018 study evaluating the transfer of Modafinil into Human Milk during Lactation. Thus, lactating mothers should take Modafinil dosage under the supervision of a doctor.
  • circleThe use of Modafinil with alcohol is unsafe and increases the risk of dizziness and drowsiness.
  • circleThe effectiveness of Modafinil in the pediatric population is not established. Therefore, it should not be used by children or people under the age of 17 years.
Modafinil Withdrawal

Sudden discontinuation of Modafinil can cause withdrawal symptoms that appear within the first 24 hours of taking the last dosage. The seven telling signs of Modafinil withdrawal include excessive sweating, chills, shakiness, nausea, disorientation, vomiting, and Confusion. Tapering off Modafinil, which includes gradually lowering the dose before completely stopping it, can help manage and reduce the occurrence of withdrawal symptoms.

Comparison Of Modafinil Products

When it comes to enhancing wakefulness and cognitive function, Modalert and Modvigil are two popular Modafinil options. While both brands are formulated with an identical active compound and have earned their reputation as a trusted Nootropic choice, a few distinct similarities and differentiations listed here can make it easier to decide which one suits your needs best.

Comparison Criteria Modalert Modvigil
Active ingredient Modafinil Modafinil
Price $1.25 per pill $0.90 per pill
Manufactured by Sun Pharma, India HAB Pharma, India.
Effectiveness Excellent Good
Onset of action 30 minutes 30 minutes
Key Customer Benefits Of Mymodalert
  • circleStringent quality check of all products.
  • circleFree pills on reorders.
  • circleRefilling reminder sent.
  • circle24x7 customer service.
  • circleMedications are available without a prescription.
  • circleEasy and hassle-free return and refund policy.

FAQ

faq

Modafinil can enhance cognitive performance in domains like memory, executive functions, and attention, increasing alertness and response accuracy.

The recommended dose of Modafinil for Shift Work Sleep Disorder is 200 mg, which should be taken 30 minutes or an hour before work.

Modafinil is unsafe for long-term use because it can cause physical and psychological dependency.

Modafinil-induced improvement of cognitive performance has been explored in several clinical trials.

Battleday and Brem, 2015 suggest that using Modafinil can enhance cognitive functioning, thus improving memory, attention span, response time, and executive functioning of the brain. It is also known to improve users' spatial planning and Stop-Signal Reaction Time (SSRT).

Modafinil improves attention and focus by affecting various neurotransmitters in the brain, including dopamine, serotonin, glutamate, histamine, and GABA.

A study by Charles S. Price, 2005, suggests that Modafinil has antidepressant properties. It can also be taken as an adjunctive treatment with the first line of antidepressants for treating bipolar and unipolar depression.

A few studies also suggest that Modafinil induces an anxiolytic effect that helps manage anxiety symptoms. However, in some people, Modafinil is known to cause anxiety. Thus, the intake of Modafinil should be done under the supervision of a doctor.

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