Modafinil effects

Hermant J, Rambert FA, Duteil J. Awakening properties of modafinil effect on nocturnal activity in monkeys after acute and repeated administration. Psychopharmacology 1991 103 28-32. 

It has been suggested that modafinil increases wakefulness by activating ai noradrenergic receptors or hypothalamic cells that contain the peptide hypocre-tin [3], or that it may act by modulating the GABAergic tone that might lead to an increased dopamine release in the nucleus accumbens. On the other hand, modafinil does not have any effect in DAT knockout mice. 

Wesensten, N. J., Killgore, W. D. Balkin, T. J. (2005). Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation./. Sleep Res. 14 (3), 255-66. 

Willie, J. T., Renthal, W., Chemelli, R. M. et al. (2005). Modafinil more effectively induces wakefulness in orexin-null mice than in wild-type littermates. Neuroscience, 130, 983-995. 

Some CNS stimulants have an effect on the same systems that are involved in wakefulness, including glutamate-, NE-, DA-, 5-HT-, histamine-, hypocretin- and ACh-containing neurons. This group includes molecules such as cocaine, amphetamine, and nicotine. The sleep-promoting systems are concentrated in the medial part of the brainstem, dorsal reticular substance of the medulla, anterior hypothalamus, and basal forebrain (Jones 2005). Other stimulants, such as caffeine and theophylline, block some sleep-inducing mechanisms. Modafinil is also a CNS stimulant with an unknown mechanism of action. 

Akaoka H., Roussel B., Lin J. S., Chouvet G., Jouvet M. (1991). Effect of modafinil and amphetamine on the rat catecholaminergic neuron activity. Neurosci Lett. 123, 20-2. 

Side effects of modafinil include headache, nausea, nervousness, and insomnia. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

Modafinil (Provigil). The newest stimulant, modafinil, is not, pharmacologically, a true stimulant. Nevertheless, it is an effective treatment for narcolepsy at doses from 200 to 400mg/day. Several studies indicate that modahnil has little potential for abuse and is easier to tolerate than other stimulants. Modafinil has been studied in the treatment of ADHD. Though not approved for marketing by the FDA at the time of this writing, it may gain the indication in the near future. 

Modafinil (Provigil) Analeptic Tab 100, 200 mg 200 mg qAM max 400 mg qAM. Nausea, headache. May reduce effectiveness of oral contraceptives. 

Comparisons of modafinil with agents that have proven effective in narcolepsy, including methylphenidate, pemoline, and dextroamphetamine, are needed to clarify its relative safety and efficacy, and place in therapy... 

Modafinil is a substrate for the cytochrome P450 (CYP) enzyme 3A4. It is also induces CYP 1A2, 2B6, and 3A4 and can decrease the serum levels and effectiveness of substrates for these enzymes. 

Amphetamines and related psychostimulants, modafinil and caffeine (ingested as capsules or as caffeinated drinks), produce feelings of increased energy and activity. These effects are particularly pronounced if subjects are engaged in strenuous or monotonous activities of longer duration. According to some reports, there seems to be a minority of subjects who show negative responses to stimulants and may feel tired, listless and occasionally even depressed (Corr and Kumari, 2000). 

Stimulants, if taken in the evening, delay sleep onset, impair the continuity of sleep at low doses and curtail its duration at higher doses (Fig. 3.7). Amphetamine-like stimulants and caffeine have different effects on REM sleep, which is unchanged after caffeine but dose-dependently reduced after amphetamine. Modafinil at single doses of 100 and 200 mg has only weak effects on the sleep polygram, with a pattern similar to that of amphetamine. 

Drugs That Interfere with Hormonal Contraceptives Concomitant use of HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John s wort with hormonal contraceptive agents may reduce the effectiveness of the contraception and up to one month after discontinuation of these concomitant therapies. Therefore, women requiring treatment with one or more of these drugs must use two other effective or highly effective methods of contraception or abstain from heterosexual sexual contact while taking thalidomide... 

Minzenberg MJ, Carter CS Modafinil A review of neurochemical actions and effects on cognition. Neuropsychopharmacol 2008 33 1477. [PMID 17712350]... 

Effects of modafinil on residual sleepiness in OSA patients treated with nCPAP Effects of bright light Sleep history and apnea severity in commercial truck drivers Effects of alcohol Sedating effects of melatonin... 

Psychomotor vigilance task performance has also been shown to be sensitive to reduced behavioral alertness associated with obstructive sleep apnea syndrome (OSAS), and the efficacy of interventions for OSAS. Performance of patients with OSAS is impaired on tasks that rely on the ability to sustain attention (85,86). As a measure of behavioral alertness, PVT performance has been demonstrated to be a sensitive method for assessing the attentional capability of patients with OSAS (32,87,88). Kribbs and colleagues (89) found that PVT performance and sleepiness, measured by the MSLT, both reflected the benefits of CPAP use (reduction in respiratory events during sleep). Similarly, the PVT has been used to demonstrate the positive effects of modafinil (a wake-promoting compound) on the capacity to sustain attention in a group of OSAS patients (34). 

Dinges DF, Weaver T. Effects of modafinil on sustained attention performance and quality of life in OSA patients with residual sleepiness while being treated with nCPAP. Sleep Med. 2003 4 393-402. 

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