What is Modafinil?

Modafinil (English name Modafinil) is an awakening enhancer that is used to treat disorders such as narcolepsy, shift sleep disturbances during work, and excessive daytime sleepiness associated with obstructive sleep apnea. Modafinil is also widely used outside of indications as a cognitive enhancer. Although the mechanism of action of Modafinil is not yet clear, this substance appears to be a selective, relatively weak, atypical dopamine reuptake inhibitor. However, this may not be the only mechanism. ^[1]

Introduction to Modafinil Compounds

Because of the addictive nature of modafinil, it is strictly controlled in mainland China, Taiwan, the United States and other places, and it is a prescription drug in most countries. Another drug, Amodafinil, is an active chiral isomer extracted from Modafinil.

Modafinil Basic Information

Chinese name: Modafinil

Chinese alias: 2-[(diphenylmethyl) sulfoxide] acetamide; Modafinil; Modafinil;

English name: Modafinil

English alias: DEP 1538; Modaphonil; Modiodal; CEP 1538; Provigil;

CAS number: 68693-11-8

Molecular formula: C ₁₅ H ₁₅ NO ₂ S

Molecular weight: 273.35000

Exact mass: 273.08200

PSA: 79.37000

LogP: 3.57600

Modafinil Properties

Melting point: 164-166 ° C ^[2]

Modafinil Modafinil related drug label information

Modafinil pharmacological effects

Modafinil can increase central excitability in normal people. EEG monitoring from the 1st hour to the 22nd hour after oral modafinil showed that the / value reflecting the level of alertness increased, and occasional microsleep waves Almost completely suppressed. For people with sleep deprivation, sleep deprivation can cause people's alertness and work ability to decline. Taking Modafinil can effectively improve this situation. Studies have shown that after a full night of sleep deprivation, volunteers taking 200 mg modafinil had significantly higher psychomotor performance than the placebo group; during periods of up to 60 hours of sleep deprivation, taking Mo every 8 hours Dafenib 200 mg can still maintain the center of sleep deprivation in a certain state of excitement, which enables them to maintain considerable alertness and ability to work. Modafinil also has a certain neuroprotective effect. Studies with animal models of brain injury have found that modafinil can effectively antagonize the production of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The neurotoxic effect makes the symptoms significantly relieved. Modafinil's neuroprotective effect has also been confirmed in the striatum mechanical injury model and the ischemic injury model, respectively. Modafinil's central excitatory effect is related to the reduction of the inhibitory transmitter transmitter amino-aminobutyric acid (GA BA) in the brain, and is regulated by serotonin (5-HT) and norepinephrine. The study found that the central excitatory effect of modafinil may be through increasing glutamine synthetase, thereby reducing GABA production, and promoting the detoxification function and energy metabolism of nerve cells.

Modafinil Pharmacokinetics

This product is quickly and completely absorbed after oral administration, and the plasma concentration reaches a peak in about 2 to 4 hours. Food does not affect the bioavailability of this product, but it can delay the absorption of the drug and delay the peak concentration for 1 hour. This product is widely distributed in the body, the apparent volume of distribution is about 0.9L / kg, which is higher than the total body fluid O.6L / kg. Plasma protein binding rate is 60%, which mainly binds to plasma albumin. After daily administration of 200 mg, the plasma drug concentration did not affect the plasma protein binding of warfarin, diazepam, and propranolol. Modafinil is metabolized in the liver by CYP3A4 of the cytochrome P450 system. Therefore, combined use of CYP3A4 inducers or inhibitors will affect the blood concentration of this product and the period of action. This product is metabolized by the liver to produce two main metabolites, modafinilic acid and modafinil sulfone, which have no therapeutic effect. Metabolites account for 90% and less than 10% of the unmetabolized parent drug. The drug is excreted through the kidney, and the elimination half-life of the drug is 10-15 hours. The drug clearance rate of young women is higher than that of young men, and the clearance rate of elderly people is significantly lower than that of young people.

Modafinil indication

For narcolepsy, depression, idiopathic drowsiness or narcolepsy with excessive sleep during the day.

Modafinil clinical application

1. Treatment of narcolepsy: narcolepsy is a central nervous system disease of unknown cause. Its main symptoms are inability to stay awake or alert during the day, uncontrollable sleep episodes and sudden onset, and patients often cannot control themselves. Sleep and cannot live normally. Modafinil, as a new type of wakefulness drug, can help patients get rid of drowsiness during the day and maintain normal work, but there will be no adverse reactions such as abnormal excitement. The most ideal drug for sleep disorders. Studies have shown that modafinil can effectively improve symptoms and significantly reduce the amount and duration of sleep during the day without affecting the time and quality of sleep at night. Modafinil was orally administered to 18 patients with spontaneous narcolepsy and 24 patients with narcolepsy. The daily dose was 200 to 500 mg / day. The results showed that the patients with spontaneous narcolepsy and narcolepsy had sleep onset and fatigue. Sleep decreased significantly, with total effective rates of 83% and 71%, respectively. Modafinil can also combat psychomotor disorders caused by sleep deprivation and improve cognitive function. It has no effect on the initiation, maintenance, awakening and sleep composition of night sleep, nor does it affect early morning behavior and daytime nap.

2. Treatment of alcoholic organic encephalopathy syndrome: Modafinil can also be used to treat alcoholic organic encephalopathy syndrome. Some people use modafinil to treat alcoholic organic encephalopathy syndrome. Clinical psychological tests and neurophysiological studies have been conducted. The results show that modafinil has increased excitability after daily medication, and the clinical treatment rate is 85%. The effective dose of this product is 200-400 mg per day, taken twice in the morning and in the middle.

3. Enhance the therapeutic effect of antidepressant drugs: Modafinil's low addiction makes it very promising to be a substitute for other stimulants and a promising antidepressant enhancer.

4. Anti-tremor paralysis and neuroprotective effect: Studies on animal models of brain injury have confirmed that modafinil has a certain neuroprotective effect.

5. For the treatment of attention deficit / hyperactivity disorder: Clinical evidence shows that modafinil improves children with attention deficit / hyperactivity disorder (ADHD).

Modafinil contraindications

1. Those who are allergic to this product are prohibited. 2. Patients with left ventricular hypertrophy, ischemic ECG changes, chest pain, arrhythmia, or mitral valve prolapse with clinical manifestations, and patients with recent myocardial infarction and unstable angina pectoris are contraindicated.

Modafinil precautions

This product has great safety, has no effect on blood pressure and heart rate, has no adverse reactions such as increased activity, tolerance or rebound sleepiness, and has no potential addiction. The main adverse reactions are nausea, nervousness and anxiety, and mild to moderate headache may occur if the dosage is increased too quickly. Therefore, medication should start with a small dose (50-100 mg daily) and increase 50 mg every 4 to 5 days until the optimal dose (200-400 mg daily). Patients with severe liver damage will be halved in dose, renal insufficiency and elderly patients should be dosed as appropriate. Patients with left ventricular hypertrophy, ischemic electrocardiogram changes, chest pain, arrhythmia, or clinically manifested mitral valve prolapse Patients with myocardial infarction, unstable angina pectoris or history of mental illness are contraindicated or used with caution.

Modafinil is generally well tolerated. The most common adverse reactions include insomnia and loss of appetite.

According to preliminary findings released by researchers at the 15th American Symposium on Psychiatry and Mental Health, although Modafinil is only approved for the treatment of excessive daytime sleepiness associated with narcolepsy, according to the latest findings, Modafinil can also significantly improve children with attention deficit hyperactivity disorder (ADHD). Joseph Biederman, a professor of psychiatry from Harvard Medical School, selected 248 children with ADHD aged 6 to 13 years and then divided them into groups, given four different doses of modafinil or placebo for treatment. . The Modafinil treatment group includes the 300 or 400 mg group once daily and the morning and noon groups, respectively, including 100 mg / 200 mg, 200 mg / 100 mg, 300 mg / 0 mg, and 200 mg / 200 mg. About a third of children are treated with stimulants during the first 30 days of treatment. The initial evaluation of the treatment effect was completed by the teacher with the ADHD rating scale IV, which includes 18 items to evaluate the behavior of children. The results of the study showed that ADHD symptoms were reduced in all patients receiving Modafinil. Among them, patients taking 300 mg modafinil once a day were more effective.

Overall, about 60% of the children in this study had improved symptoms with modafinil, compared to only 30% in the placebo group. The analysis of the ADHD / DSM-IV rating scale also confirmed the teacher's evaluation results. The tester's ADHD / DSM-IV rating scale included 26 evaluation indicators that evaluated a variety of behavioral changes including inattention, temper tantrums, and mood changes. Modafinil is generally well tolerated. The most common adverse reactions include insomnia and loss of appetite.

Modafinil adverse reactions

1. Systemic headache, back pain, flu-like symptoms, chest pain, chills, neck stiffness. 2. Cardiovascular hypertension, tachycardia, palpitations, and vasodilation. 3. Digestive system nausea, diarrhea, indigestion, dry mouth, loss of appetite, constipation, abnormal liver function, flatulence, oral ulcer formation, dry mouth, thirst. 4. Increased eosinophils in the blood lymphatic system. 5. Metabolic edema. 6. Nervous system nervousness, insomnia, anxiety, dizziness, depression, paresthesia, drowsiness, hypertension, dyskinesia, hyperkinesia, agitation, confusion, tremor, emotional instability, dizziness. 7. Respiratory rhinitis, pharyngitis, lung disease, epistaxis, asthma. 8. Sweating skin, herpes simplex. 9. Specific sensation amblyopia, abnormal vision, reversed taste, eye pain. 10. Urinary system dysuria, hematuria, pyuria.

Modafinil dosage

Oral, 200-400mg daily, taken in the morning. For patients with severe liver dysfunction, the dose should be reduced to 1/2 of the normal dose.

Modafinil drug interactions

1. Carbamazepine, itraconazole, ketoconazole and other CYP3A4 inhibitors or phenobarbital and rifampicin CYP3A4 inducers used simultaneously with modafinil may change the blood concentration of this product. 2. This product is a CYP3A4 inducer, which can reduce the blood concentration of cyclosporine by 50%, and can also reduce the blood concentration of theophylline. 3. This product is a reversible CYP2C19 inhibitor, which increases the blood concentration of warfarin, diazepam and phenytoin sodium. This product can also increase tricyclic antidepressants, chlorpromazine, omeprazole , Lansoprazole, propranolol and other drugs. When used simultaneously with the above drugs, the dose needs to be adjusted accordingly, and the blood drug concentration should be monitored. 4. This product can reduce the efficacy of steroidal contraceptives. Other contraceptive measures should be taken during the use of this product and within one month after discontinuation. ^[3]