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Modafinil 200mg Australia is structurally unrelated to amphetamine and has a different profile of central effects. It has a low affinity for the DAT transporter and no clear binding to other monoamine or neuropeptide receptors, nerve membrane ion channels, or second messenger systems (see Table 1).
A large randomized placebo-controlled study of shift work sleep disorder found that modafinil significantly reduced performance decrements during extended wakefulness with adverse circadian phase working hours without affecting subjective alertness.
Sleep Patterns
The circadian rhythm is a 24-hour cycle of bodily functions such as body temperature, hormone production, and sleep. Circadian rhythms are present in nearly all organisms ranging from cyanobacteria to humans. These rhythms are coordinated by the suprachiasmatic nucleus (SCN) in the hypothalamus, a part of the brain. The SCN integrates photic and non-photic environmental time cues to create sleep/wake patterns that are optimized for survival.
While many factors affect the quality of our sleep, one of the most important is how our sleep patterns match up with our natural 24-hour cycle. If our sleep-wake patterns are too far out of sync with our bodies’ internal clocks, it can result in serious health problems. People who suffer from circadian rhythm sleep disorders (CRSD) may experience difficulty falling asleep and staying asleep, fatigue during the day, memory problems, and poor cognitive performance.
A variety of factors can contribute to this, such as a lack of sleep or an irregular schedule, over-indulging in caffeine and other stimulants, and eating at times that are not conducive to good health. It is best to try to stick with a routine and only make changes gradually. For example, if you want to adjust your sleep/wake pattern by an hour or two, do so over several days instead of changing the schedule abruptly.
Other factors that can cause CRSD include shift work or jet lag. Modafinil can help restore the normal sleep/wake pattern and improve performance during the day.
Sleep Apnea
The circadian alerting system is a set of neurochemical processes that promotes wakefulness and inhibits sleep. Circadian rhythm sleep disorders occur when a person’s external schedule of sleep and wakefulness is out of sync with the internal circadian pacemaker, such as in shift work, jet lag, or delayed sleep phase syndrome. Modafinil, available under the brand name Provigil, is a central nervous system stimulant that acts as a wakefulness agent. It has also been shown to reduce fatigue in multiple sclerosis patients and may improve symptoms of depression.
A small number of studies have reported that modafinil (Modawake 200 mg) increases Fos-immunoreactivity in identified orexin cells in the perifornical area of the brain. It does not, however, affect extracellular striatal acetylcholine, and it induces wakefulness more potently in orexin-knockout mice than in wild-type mice (Chemelli et al, 1999; Scammell et al, 2000).
Another study of modafinil found that a single dose of 400 mg a day was sufficient to reduce errors on the Wisconsin Card Sort Test and interference on the Stroop test in healthy adults following 85 hours of sleep deprivation (Wesensten et al, 2005). This finding was independent of the effect on cognitive performance of modafinil.
Treatment of medication-free narcoleptics with modafinil titrated to 400 mg/day for 3 weeks remediated the decrement in a-2 and b-2 power in a vigilance-controlled EEG measured by low-resolution brain electromagnetic tomography, LORETA (Saletu et al, 2004). These effects were localized to frontal and anterior cingulate cortices.
Mood Disorders
Mood disorders are mental health conditions that involve long periods of excessive sadness (depression) or excessive elation (mania). Sadness is a normal reaction to loss, defeat, disappointment, trauma, or catastrophe. However persistent, disabling depression is different from the sadness that may occur as a result of a death or a divorce and is called grief or bereavement.
Symptoms of depression include a lack of interest in usual activities, feelings of worthlessness or guilt, changes in appetite, sleeping more than usual, a feeling of hopelessness, and low energy. These symptoms may come on suddenly or become worse over time and interfere with work, family life, and social activities.
Mania, on the other hand, is characterized by feelings of elation or happiness that are out of proportion to the situation and that are accompanied by inflated self-esteem or grandiosity, racing thoughts, impulsive behavior, and hyperactivity. During a manic episode, a person may be irritable, argumentative, or easily distracted and may be at risk of harming himself or others.
Mood disorders can also be related to other medical conditions, such as neurological diseases like ALS and Parkinson’s disease, or chronic illnesses, such as heart disease and cancer. It is important to seek treatment for mood disorders as soon as possible, as they can lead to severe disruptions in daily life and can increase the risk of suicide.
Fatigue
Many individuals with various illnesses experience a lack of restful sleep and feel fatigued. In some cases, this fatigue may be relieved with the use of wakefulness-promoting agents such as modafinil. In one randomized study, a small sample of patients receiving modafinil showed a marked improvement in clinical measures of fatigue compared to those given placebo. This included a shorter auditory P300 latency and a longer Letter-Number Span test. However, the authors of the study caution that their results must be considered in light of the small sample size and other potential confounding factors.
Modafinil is thought to increase central neurotransmitter systems involved in the modulation of cognition and mood. For example, it has been shown to increase extracellular levels of DA in the prefrontal cortex (PFC) and rostromedial hypothalamus of anesthetized rats. It also increases extracellular NE in PFC and potentiates the NE-induced inhibition of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO) in anesthetized rats.
Modafinil may also increase serotonin levels by increasing the sensitivity of raphe 5HT receptors to dopamine. In anesthetized rats, the vigilance-promoting drug has been found to enhance the increased extracellular serotonin induced by the antidepressants fluoxetine and imipramine through an alpha 1-adrenergic mechanism (Duteil et al, 1979). In addition, it has been shown that the vigilance-promoting agent modafinil amplifies the increase in dialysate cortical serotonin levels induced by the administration of the atypical antipsychotic medications clonidine and haloperidol, but not by phenytoin, a non-atypical MAOI. Read More Blog…
