Active Ingredient: Modafinil
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Modafinil is a prescription drug for patients with narcolepsy, increases concentration of attention and relieves drowsiness, also enhances the perception and memory capacity. Modafinil as a biologically active additive takes an honorable place among nootropic drugs. Modafinil is a drug that relieves sleepiness in the daytime and for the treatment of narcolepsy. It is possible to improve perception by stimulating neurotransmitters in the brain, used to improve mental abilities.
Provigil or benzhydryl sulfinylacetamide is a central stimulant (psychostimulant). The substance has been approved by the FDA for the treatment of narcolepsy (a disease characterized by sudden and uncontrolled bouts of deep sleep, fatigue or excessive drowsiness), sleep apnea, and sleep disorders caused by changes in the mode of operation.
The quality of the drug was tested, including, as a remedy for the treatment of Alzheimer’s disease, depression and attention deficit disorder. Modafinil belongs to a group of drugs known as eugeroics (stimulants) that promote mental alertness and attention.
One of the known mechanisms of action of these drugs is the agonism of alpha-1-adrenergic receptors, as a result of which drugs affect the mood, increasing energy by increasing the release of dopamine in the central nervous system. This also leads to changes in the levels of GABA and glutamate. In studies of modafinil as a stimulant, the advantages of the drug were shown in comparison with amphetamines.
To begin with, the substance is supposed to have a much lower potential for abuse due to the fact that its effect does not cause the same euphoria. In addition, the drug has a lesser effect on peripheral CNS stimulation (that is, it shows fewer side effects), has minimal effect on blood pressure, does not cause sleep interruptions (no hangover or need to catch up on sleep), and, according to clinical trials, has a more reliable security profile.
The drug is used even by the US military as an energy stimulant for pilots and soldiers needed to work for long periods of time without sleep. This is not so strange as it may seem at first glance, since in the past military pilots and soldiers widely used dexedrine (amphetamine) during long periods of lack of sleep.
Provigil has been tested in recent combat situations, such as Afghanistan and Iraq, and may in the future be officially recognized as a special preparation for the military.
Recently, modafinil has gained popularity among competitive athletes. They use it not just as a medicine for “vivacity”, but as a stimulant, increasing productivity and endurance. This use is likely to be a surprise to the developers of this drug, as previously it was reported that this “gently” vigilant drug does not have strong stimulatory effects, and can not improve athletic performance.
Recent research contradicts these statements. A study in Canada showed that taking Provigil can provide significant sports benefits. In a double-blind study, 15 male volunteers took the drug at a dose of 4 mg per kg of body weight (equivalent to 200 mg for a person weighing 220 pounds), or a placebo.
Three hours after the meal, aerobic exercises were performed on the veloergometer at 85% of the maximum aerobic capacity, until exhaustion. Taking Provigil, men could exercise for significantly longer periods of time (up to 30% longer), and used more inhaled oxygen for exercise. Also reported was a decrease in subjectively perceived tension, resulting in increased productivity during training.
Provigil was developed by Lafon Laboratories in France. In 1998, the drug was approved by the FDA for sale in the United States, where it was sold under the brand name Provigil.
Provigil also occurs in the international market under this and several other trade names, including Modiodal, Vigil, Alertec and Modasomil. Although the drug has favorable safety indicators, in the United States for some time it was considered a drug capable of provoking possible abuses.
Currently, Provigil is on the list of IV controlled substances, along with Valium and Xanax. Thus, its use for non-medical purposes is limited by significant legal sanctions for possession and import of the drug. The drug has a fairly wide medical use, including sleep disorders associated with changes in the mode of operation.
The drug is often prescribed by prescription. In 2000-2004, Modafinil became popular among competitive athletes, before sports authorities did not begin to worry about the use of the drug. In 2004, a doping scandal erupted in connection with the company Valco, when it became known that many of the athletes who gave a positive result for the use of tetrahydrogestrenone, also used Provigil.
After this, the IOC prohibits the use of Modafinil, and a number of studies have developed a methodology for detecting this chemical in the urine. Now this testing is part of the standard survey of athletes before the Olympic Games. Most other international sports bodies have followed the example of the IOC to ban and test Modafinil.
Since then, the drug has lost its appeal as “invisible” in checks, although it is still used by many athletes who do not undergo random urine testing.
Provigil is most often supplied in the form of tablets of 100 mg and 200 mg each.
How to use?
The drug “Modafinil“, the instruction to which must necessarily be attached, should be prescribed only by a doctor. The doctor also prescribes the necessary dose for a particular patient. Usually the specialist prescribes 2-4 tablets per day. The drug should be taken in the morning and at lunch.
If a patient has arterial hypertension, then during treatment with Medafinil medication, the price of which will be indicated below, he needs to control blood pressure. If the patient has liver function, then the dose is reduced to 0.1-0.2 g per day.
The half-life of modafinil is 13-15 hours, and the concentration in the serum in the equilibrium state reaches 2 days after the onset of admission. The half-life of the S-isomer of modafinil is 4-5 hours, whereas in the R-isomer of modafinil, the period is longer (15 hours) and thus the intake of armodafinil is almost equivalent to taking Provigil.
The results of the experiments showed that the concentration of ardomafinil in the blood is 18% higher than in the case of modafinil (5.44 +/- 1.64 mg / ml versus 4.61 +/- 0.73 mg / ml) and accumulates in a shorter time interval (1.8 hours against 2.5 hours), and the total concentration of ardomafinil in the urine is higher by 32-40%.
Although both variants of modafinil (modafinil and armomafinil) have the same half-life, the effect of armomofinil on the body is more pronounced (according to the content in the urine and blood).
According to the immunocytochemistry data of the c-Fos gene (the gene responsible for the stimulation response and detected by neural stimulation or sleep deprivation), the introduction of modafinil to cats caused a sharp activation of the c-Fos gene in the anterior hypothalamic nucleus and adjacent areas and was weak in the suprachiasmatic nucleus and minimal activation of the gene in other areas, for example, in the cerebral cortex or striatum.
Such a pinpoint activation of the hypothalamus was noticeable everywhere, and amygdala was involved in the process. Studies in humans showed clear differences between the effects on humans of modafinil and amphetamine.
In contrast to the effects of amphetamine or methylphenidate – excessive vivacity (which indicates a widespread neuronal activation), modafinil also acts selectively: the hypothalamus and amygdala.
Provigil is able to increase extracellular levels of dopamine in the prefrontal cortex in rats and in the caudate nucleus in dogs.
Modafinil acted on dopamine and noradrenaline receptors (in the striatum), and the absence of such an effect in mice was associated with the disappearance of the effects associated with sleep, which was confirmed by the fact that the Provigil exposure mechanism does affect sleep.
Recent studies have shown an insufficient effect of modafinil on dopaminergic systems, which may be due to a lower dosage used previously.
The invigorating effect of modafinil is significantly weakened by antagonists of adrenergic receptors (alpha and beta subunit), however, inhibition of catecholamine synthesis by α-methylparathyrosine does not reduce the effect.
In people with deficiency of orexin (nalotics) modafinil shows good results, directly affecting orexin neurons. This effect has had the greatest effect on mice with deficiency, the effect of modafinil on the orexin system of healthy individuals and humans is unknown. 3.5.
Sedative and stimulatory effects The results of some studies are negative for the effects of modafinil during intentional sleep deprivation, since the effect of 300 mg of Provigil during sleep deprivation is equivalent to taking 20 mg of D-amphetamine.
However, it was noted that the deterioration of self-control (the ability to accurately assess yourself and your environment) changes toward excessive self-confidence (an incorrect assessment of what is really capable of). These studies continued for 64 hours (two nights without sleep) with a single dose of Provigil every 15 hours.
Taking modafinil before going to bed can seriously change the sleep cycle and lead to subsequent lethargy, and can also cause side effects (worsening of mood and mental abilities). Recurrent hypersomnia is a phenomenon in which, after the end of the action of drugs against drowsiness, it tends to sleep even more than before they are taken.
Unlike amphetamine-based drugs, modafinil does not cause this phenomenon in cats, rats and mice. People who did not sleep for 64 hours and took modafinil, this phenomenon is also not seen, in contrast to the results when taking D-amphetamine. Provigil does not cause recurrent hypersomnia. Exacerbation of attention is observed with sleep deprivation for 10-12 hours after a single intake of 300 mg of modafinil, which is equivalent to 20 mg of D-amphetamine.
The dose of Provigil 300 mg from drowsiness is equivalent to a 20 mg dose of D-amphetamine. The brain cycle of sleep is the balance of the “ascending activating system”, consisting of activating neurotransmitters (catecholamines, acetylcholine, nuts, etc.) and neurotransmitters (GABA, galanin), which suppress stimulation and contribute to falling asleep. Changing levels of activation and suppression of neurotransmitters forms a kind of cycle “switch-on-switch”.
In general, the regulation of the cycle of vivacity and rest depends, on the one hand, on the daily biorhythm caused by the suprachiasimatic nucleus, and on the other hand, on the homeostatic need for sleep that occurs during wakefulness. Provigil is able to contact with various stimulant systems, including serotonergic, noradrenergic, dopaminergic, glutaminergic, histaminergic, oroxynergic and GABAergic pathways of metabolism.
During some studies, Provigil was used in the treatment of a number of other diseases, and it was found that the side effect of insomnia lasted longer than in the placebo group, and that modafinil taken at bedtime did not let the experiment participants fall asleep. The use of modafinil promotes mental stress.
Memory and thought processes
In healthy people, when taking 100-200 mg of Provigil 2 hours before the test (arithmetic test), the memory properties, spatial-visual planning and reaction rate were improved. Short-term memory and accuracy of information processing improved after taking 200 mg of modafinil. In addition to the above, improvements are observed when performing the task as a whole – increasing motivation, enjoying the work done.
In methamphetamine-dependent cognitive impairments, the dose of Provigil in 400 grams, broken down for 3 days, is able to improve the properties of short-term memory, which was previously not possible, but a single dose of 200 mg modafinil is not capable of causing such an effect.
Impact on the appetite
Researchers who condemn the drug, sometimes report a violation of appetite as a side effect in 16% (164 people). Some researchers consider this fact the cause of weight loss within a week, however, statistically.
Provigil is unable to activate the neural pathways of metabolism, which occurs with dependence, and therefore it is believed that the drug has a low threshold of habituation with respect to other similar drugs. It is unlikely that modafinil will be used as a drug in the environment of drug addicts.
Provigil is able to help alleviate the breakdown in methamphetamine-dependent, alcoholics and gamers, but the effect of exposure varies. Provigil also reduces the impulsivity of the dependent, but this effect only affects the subjects whose impulse threshold before the experiments was already low.
>>> The effect of the drug on people with certain diseases <<<
One-time administration of ardomofinil (250 mg) in patients with multiple sclerosis showed improved mnemonic reproduction, the effect was comparable to the placebo effect, but the fatigue, the ability to focus and the processing speed of the information did not affect the drug in any way.
Precautionary measures. Toxicology
The tests revealed the following adverse effects of the drug – headache, dizziness, diuresis, heart palpitations, tachycardia, anxiety, nervousness, gastrointestinal problems such as nausea, and dry mouth and abdominal pain. Apart from the above, Provigil is considered a well tolerated drug.
Common side effects of modafinil include insomnia and decreased appetite.
Provigil side effects
Side effects Provigil, as a rule, associated with stimulation of the central nervous system and may include nervousness, insomnia, trembling, euphoria, personality changes and arousal. The drug can also cause gastrointestinal disorders such as nausea, vomiting, abdominal pain, dry mouth, anorexia and headache.
Hypertension, heart palpitations or abnormal heart rhythms may also occur.
In rare cases, an allergic rash, an increase in alkaline phosphatase or a disorder in voluntary movements may occur.
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