By jahanzaib 
Many people take modafinil to increase their cognitive abilities. Students, for example, rely on the drug to improve their ability to learn and recall information. But does it work?
In this study, participants were given either a placebo or 200 mg of modafinil. Plasma modafinil concentrations and dopamine transporter blockade were measured in both groups.
Dopamine
Modafinil Australia Online is a central nervous system stimulant with a relatively low abuse potential. It is thought to act by inhibiting dopamine reuptake and by activating glutamatergic circuits. It is also a weak alpha 1B-adrenergic receptor agonist. Its effects can be reversed by prazosin, a 1-adrenergic antagonist.
Modafinil is eliminated primarily in the liver by amide hydrolysis and to a lesser extent by cytochrome P450-mediated oxidation. Its excretion is rapid and less than 10% of the oral dose is excreted as an unchanged drug. Its elimination is slower in the elderly and individuals with hepatic or renal impairment.
Studies of cognition and neuroanatomy have used fMRI to evaluate the effects of modafinil in humans. One fMRI study of narcolepsy patients found that modafinil improved performance on the Cambridge Neuropsychological Test Automated Battery and visual analog scales of subjective feelings of fatigue. However, the results were not consistent with those of a placebo.
Another fMRI study found that modafinil increased activation of the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex in response to cognitive demand. This was associated with an increase in the ability to perform a digit symbol substitution task.
This study found that the performance improvement was mediated by an indirect interaction between DLPFC and orexin. In addition, it was correlated with the direct binding of modafinil to the DAT and indirect inhibition of norepinephrine uptake in these areas.
Serotonin
Modafinil is one of the wakefulness-promoting agents that are used to treat narcolepsy. It works by activating a group of neurotransmitters called orexins, which are related to the hormone dopamine. It also affects a family of sleep-suppressing peptides known as orexins. By binding to these neurotransmitters, modafinil increases the production of dopamine and decreases g-aminobutyric acid (GABA) in the brain. It also blocks the reuptake of the norepinephrine and serotonin transporters.
Waklert 150 mg may have fewer side effects than traditional psychostimulants and does not increase the risk of addiction. However, it can cause a rapid recurrence of REM sleep-related symptoms in some patients who are switched from amphetamines. These symptoms are usually controlled with the addition of anti cataplectic drugs.
Modafinil has been shown to improve cognitive function in people with narcolepsy. It can help to keep them awake during the day and can prevent them from falling asleep during work. It can also reduce excessive daytime sleepiness in people with obstructive sleep apnea, shift-work sleep disorder, and circadian rhythm sleep disorders.
Twelve individuals with affectively stable bipolar disorder were randomized to receive modafinil or placebo adjunctive to their prescribed mood stabilizer. They underwent a week of fMRI sessions to measure the interaction between the drug and their task performance.
A blood sample was drawn to measure serum modafinil levels before each fMRI session. Activation of the right amygdala and lateral PFC were reduced with modafinil, while activity in the left PFC and pregenual ACC was enhanced.
Glutamate
The stimulant properties of modafinil are associated with its inhibition of the reuptake of glutamate. Glutamate is an amino acid that has been linked to a variety of cognitive functions, including memory and attention. Modafinil has also been shown to enhance cholinergic activity in the brain. This interaction is thought to be responsible for the cognitive effects of the drug. However, the exact mechanism of action is unclear.
Several studies have demonstrated that modafinil improves prefrontal cortex function in psychiatric patients. In one double-blind placebo-controlled fMRI study, modafinil 100 mg single-dose was associated with greater activation of the dorsal anterior cingulate cortex in schizophrenia patients during performance on a modified N-back task (Spence et al, 2005).
Moreover, c-fos labeling in rats showed that modafinil administration caused Fos activation in the tuberomammillary nucleus and the hypocretin/orexin neurons of the perifornical area, both of which are involved in the regulation of wakefulness.
Modafinil has a low potential for abuse, probably due to its weak stimulant and euphoric effects. It is also insoluble in water and unpalatable at high temperatures, minimizing its attractiveness as a drug of abuse, unlike cocaine or other amphetamines. It has also been used by some people without a medical prescription to overcome sleepiness in situations such as jetlag and excessive work or school workload.
Histamine
Modafinil appears to enhance cognitive function in healthy non-sleep-deprived adults. In a single-blind, placebo-controlled study, modafinil at 200 mg/day (plus concurrent atypical antipsychotics) was associated with improved performance on digit span forward and backward, spatial planning and delayed recognition memory tasks, and inhibition of prepotent responding on a version of the Pauli test (Turner et al, 2003).
The cognitive effects of modafinil are not solely mediated by central dopamine systems, however. It also increases hypocretin, histamine, epinephrine, and gamma-aminobutyric acid (GABA). Modafinil has no direct actions on these neurotransmitters but appears to inhibit their reuptake by increasing the concentration of extracellular GABA, which is released via glutamine synthetase (Tanganelli et al, 1995).
In the context of anesthesia, modafinil decreases [11C]raclopride binding to DA transporters in the locus coeruleus (LC) of anesthetized rats. This decrease correlates with reduced LC DA activity and potentiates the NE-induced inhibition of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO).
It also reduces the sensitivity to the GABA antagonists muscimol and clonidine in LC cells, suggesting that modulation of histamine and adrenergic receptors may play a role. Furthermore, in vivo microdialysis studies indicate that modafinil increases DA levels in the striatum (including nucleus accumbens) while decreasing NE availability.
Moreover, modafinil has been shown to reduce MPTP-induced nigrostriatal DA neurotoxicity while preventing the development of an oxidative stress response (Aguirre et al, 1999). It has also been demonstrated that modafinil prevents the reduction of extracellular GABA by the catecholamine neurotoxins 6-hydroxydopamine and prazosin in cultured cortical neurons.