Modafinil improves cognitive function and is associated with frontal cortex activation in animal models and humans. It is effective in a wide range of neuropsychiatric disorders, with an advantageous side-effect profile and low liability to abuse.
Pre-treatment with low doses of the a2 agonist yohimbine potentiates modafinil wakefulness and activity increases, whereas higher doses block inhibitory terminal a2 receptors and attenuate these effects (Duteil et al 1990). The mechanism appears to involve NE facilitation of glutamate release onto medial PFC pyramidal cells.
Dopamine
Buy Modafinil Australia increases dopamine levels in the brain by increasing its transport into neurons and by inhibiting its reuptake. This increase in dopamine leads to increased adenosine triphosphate (ATP) production and increased neuronal firing rate, which may enhance wakefulness. Modafinil has also been shown to improve cognitive function. This is likely to be due to the effect of the drug on frontal cortex neurotransmitters.
Dopamine also plays an important role in reward processing. Dopamine neurons monitor the difference between the reward that you expected from your behavior and the actual rewards that you receive. This information is fed to a variety of brain areas and influences motivation, decision making and reward learning. There is also evidence that dopamine plays a key role in the onset of psychosis, and some antipsychotic medications act by blocking dopamine receptors.
The vigilance-promoting effects of modafinil have been demonstrated in both humans and animals. In one study, a 3-week modafinil treatment remediated the decrement in the a-2 and b-1-3 power of evoked EEG measured by low-resolution brain electromagnetic tomography (LORETA) that was associated with placebo treatment in narcolepsy patients. The remediated effect was localized to frontal and cingulate cortical regions. In another human study, a single dose of modafinil 100 mg was associated with an improved performance on the digit span forwards and backwards and a version of the Tower of London memory task. This improvement was accompanied by reduced error rates on these tasks.
GABA
Gamma-aminobutyric acid, or GABA, sends chemical messages through the brain and nervous system to inhibit or reduce the activity of brain cells. Low levels of this neurotransmitter are associated with depression, anxiety and sleep disorders, notes McGill University. Modafinil increases the concentration of GABA in the brain and enhances the activity of a protein that degrades GABA. The drug also increases the amount of glutamate, which is converted to GABA in neurons. This increase in the glutamate-glutamine pool is probably caused by the upregulation of the mRNA for the enzyme Glutamine Synthase, which modafinil increases in rat brains (Touret et al, 1994).
Modafinil (Modalert 200 mg) has consistent effects on central glutamate and GABA neurotransmitter systems. It increases extracellular glutamate in the thalamus and, at higher doses, in the striatum and hippocampus. These increases in glutamate are associated with c-Fos activation, which is attenuated by the GABAA antagonist bicuculline.
Modafinil improves performance on a delayed nonmatching to position task in rats, an ability that is sensitive to damage of the anterior cingulate cortex and/or the mediodorsal nucleus of the thalamus (Krazem et al, 1995; Meunier et al, 1991). In another behavioral test, modafinil does not affect intersession learning but does significantly improve general alternation abilities. In both tasks, modafinil increases the performance of mice that have been treated with mammillary body agonists or with phenylethylamine.
Serotonin
Serotonin is a chemical messenger within the brain that allows nerve impulses to pass from one cell to another. It is found in the layer or membrane that surrounds each neuron. Once the signal is passed, it binds to receptor proteins on the postsynaptic cell. The receptors then change the electrical state of the neuron and cause a chemical reaction in the cell. After the cell has processed this chemical, it releases vesicles that contain serotonin into the gap between cells, known as the synaptic cleft. This can excite or inhibit the cell. Serotonin is then taken back up by the presynaptic neuron to continue the signaling process.
Modafinil has been shown to have many cognitive and psychiatric benefits, including reducing fatigue and improving performance in various clinical trials of patients with narcolepsy and obstructive sleep apnea. It also appears to improve cognitive functioning in schizophrenia patients who are taking psychotropic medications. Although single case reports have described adverse effects of modafinil in psychiatric patients, these events do not appear to be common and are usually associated with high doses and long-term use of the drug.
Several studies have found that modafinil increases extracellular levels of monoamines in the hypothalamus and the prefrontal cortex. These effects may be mediated by adrenergic and dopamine receptors. In addition, modafinil has been shown to increase acetylcholine levels in the prefrontal cortex and reduce errors on the WCST in patients with narcolepsy.
Norepinephrine
Norepinephrine is a hormone that helps control the body’s response to stress. It is produced by neurons in the prefrontal cortex and the amygdala, and is stored in vesicles that are released into the synaptic cleft when voltage-gated calcium channels are activated. Norepinephrine binds to three different receptors and can exert either stimulatory or inhibitory effects on brain cells.
When the arousal-promoting effect of modafinil is evaluated in animal models, it seems to be primarily due to changes in the activity of these catecholamine systems, rather than alterations in glutamate or GABA. In addition, it has been found that modafinil increases extracellular levels of monoamines in the prefrontal cortex and medial hypothalamus, as measured by microdialysis. Modafinil also binds to the dopamine uptake transporter in the brain, but with a low affinity.
A number of studies have evaluated modafinil for the treatment of narcolepsy and other sleep disorders, with mixed results. Modafinil appears to improve wakefulness and vigilance in these conditions, but it may not be helpful in treating the underlying cause of sleep disturbances in most cases.
A small percentage of people taking modafinil experience adverse effects such as dizziness, headache, nausea, chest pain and gastrointestinal upset. People should discuss any potential side effects with their healthcare provider. These symptoms can be mild to moderate and may last a few days after beginning treatment with the drug.
