Dose Effects on Sustaining Cognitive Function
Modafinil 200 mg has been show to induce wakefulness in both mice and humans (Arnsten et al, 2002; Broughton et al, 2003; Duteil et al, 1990; Lin et al, 1992; Willie et al, 2005). Orexin binding does not affect modafinil effects on Fos-immunoreactivity in identified orexin cells in the perifornical area of mice and rats (Chemelli et al, 1999; Scammell et al, 2000), but it does enhance extracellular striatal DA release from adenosinergic neurons in awake dogs (Wisor et al, 2001).
Adenosinergic neuronal activation is thought to promote vigilance by suppressing pre-potent responding. A study of locus coeruleus neurons in monkeys revealed. That conditioned responses of these neurons anticipated the acquisition of discriminative behavior during a vigilance task (Aston-Jones et al, 1997).
These findings suggest that adenosinergic modulation of wakefulness may be an important factor in Modafinil 200 mg cognitive enhancement. However, the mechanism by which adenosinergic modulation is responsible for vigilance improvement appears to be very complex and based on a variety of processes.
In a study of awake rats, modafinil significantly increased the levels of dialysate serotonin in different brain regions. An increase in the oxidative stress-induced release of extracellular glutamate in the medial preoptic and posterior hypothalamus accompanied this. In contrast, amphetamine significantly decreased dialysate serotonin levels in the same areas and inhibited extracellular glutamate release.
Moreover, the action of modafinil 200 mg on wakefulness is likely to involve. A biphasic interaction between adenosinergic and GABAA receptors. Adenosinergic signaling is responsible for promoting the release of neuroactive neurotransmitters. Such as dopamine and norepinephrine, from dopaminergic neurons in the striatum (Bunney et al, 1976; Bunney et al, 1984).
Another adenosinergic modulator that has been studied as a possible cognitive-enhancing agent is yohimbine. Low doses of yohimbine pre-treatment with modafinil significantly increase modafinil-induced wakefulness and activity, but higher doses decrease these effects. In addition, pre-treatment with yohimbine potentiates NE release by modafinil, suggesting that it acts to augment post-synaptic a2 receptor activation.
A small study of narcolepsy patients find that modafinil 600-mg split-dose or 400-mg split-dose. Regimens were associate with greater wakefulness throughout the evening. In this study, the proportion of patients able to maintain wakefulness for at least 20 minutes during both MWT sessions. The evening was significantly higher with 600-mg or 400-mg split-dose. Regimens than with the 200-mg once-daily dose regimen (Figure 2, Panel B).
Dose Effects on Sustaining Physical Activity
Narcolepsy is characterize by excessive daytime sleepiness and an overwhelming desire to nap during the day. The condition can also cause sleep paralysis, hypnagogic hallucinations, and automatic behaviors. Narcolepsy is a disorder that can be treate with various medications, including Buy Modalert 200 (phenylmethylsulfonyl acetamide; brand name Provigil in the United States), armodafinil, and sodium oxybate.
Narcolepsy can be classified into narcoleptic (type I) and nonnarcoleptic (type II) forms. Type I patients have recurrent naps, a mean sleep latency of fewer than 10 minutes during rapid eye movement (REM) sleep. And a CSF hypocretin level that is lower than the normal range. They are also prone to cataplexy, which is a sudden loss of postural muscle tone associate with intense emotion. They may also have other symptoms, such as a nocturnal restless leg syndrome or idiopathic hypersomnia.
In narcolepsy, wakefulness is usually achieve by a combination of a stimulant and a sleep-promoting agent. These agents have been show to have positive effects on alertness and cognitive function in narcolepsy.
The narcolepsy-modifying drug Modafinil 200 mg has shown positive effects on vigilance and cognitive function in several studies. It has also been report to increase extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of conscious rats. This effect has suggesting to be due to the inhibition of striatal, pallidal, and nigral GABA release.
This narcolepsy-modifying agent has also showing to improve executive function in other models of excessive sleepiness. It has been reporte to improve a number of tests of attention and memory in both patients with narcolepsy and shift work sleep disorder.
Moreover, the effects of Modvigil have been demonstrat to be long-lasting in patients with narcolepsy. The medication has been find to significantly reduce the time required for subjects to fall asleep during maintenance of the wakefulness test. The effects of Modafinil 200 mg were also find to be significant on a Clinical Global Impression of Change (CGI-C) assessment in both the narcolepsy and shift work disorder groups.
A randomized, double-blind study was perform to evaluate the efficacy of Modvigil in maintaining wakefulness in narcolepsy patients. Experiencing residual late-day sleepiness following a positive therapeutic response earlier in the day. Fifty-six subjects were assign to a 200-mg once-daily or split dose of modafinil. And were then administer a Maintenance of Wakefulness Test (MWT). Results were analyze using statistical methods base on two-sided comparisons with treatment as a factor and baseline value as a covariate.
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