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Modafinil for excessive daytime sleepiness in myotonic dystrophy.

The authors conducted an open-label trial of modafinil for excessive daytime sleepiness in myotonic dystrophy. Eleven patients were evaluated: two were not treated because of obstructive sleep apnea, and nine received 200 to 400 mg modafinil/day for an average of 16.4 weeks. There were no major side effects. Average sleep latency as measured by the Multiple Sleep Latency Test increased from 7.3 to 22.7 minutes ( p = 0.00013), and average Epworth Sleepiness Scale score decreased from 13.25 to 7.75 (p = 0.01028). Modafinil shows evidence of effectiveness for excessive daytime somnolence in myotonic dystrophy and should be investigated further.

Adult↗

Crystal and molecular structure of an (S)-(+)-enantiomer of modafinil, a novel wake-promoting agent.

The (+)-enantiomer of modafinil [(RS)-2-(diphenylmethylsulfinyl)acetamide], a novel wake-promoting agent, was clarified to be S-configuration by X-ray crystal structure analysis. The crystal consists of two crystallographically independent conformers that are different at the torsion angles around the sulfinylacetamide moiety, and this results from the molecular packing requirement to form a two-dimensional hydrogen-bonding network via neighboring amide groups in the crystal. The crystal structure is characterized by the formation of alternative hydrophobic and hydrophilic layers, which are formed among the symmetry-translated assemblies of diphenylmethyl and sulfinylacetamide moieties, respectively. The spatial orientation between the diphenyl and amide groups is believed to be important for the activity of modafinil.

Benzhydryl Compounds↗

Modafinil, sleep deprivation, and cognitive function in military and medical settings.

Military personnel of many professions, including health care workers, are routinely challenged with performing their duties during hours when the circadian rhythm is at its trough, namely, late night and early morning. Studies have shown that cognitive performance declines significantly during these hours. Although many pharmacologic agents have been studied in an attempt to find a safe medication to enhance alertness and cognitive function, no safe nonaddictive options have been identified. Modafinil is a novel wakefulness-promoting agent that has been shown to improve cognitive performance and promote wakefulness among shift workers. This article reviews the studies on modafinil administration and cognitive performance as they relate to military operations and the provision of health care by sleep-deprived individuals.

Benzhydryl Compounds↗

Modafinil as an adjunctive treatment to sleep deprivation in depression.

Sleep deprivation (SD) is a rapid-acting treatment for depression, but its clinical efficacy is hampered by high relapse rates after recovery sleep, and its effectiveness is reduced by the demanding effort needed for the patient to stay awake. To our knowledge, this is the first reported case of a successful treatment of depression with the combination of SD and the wakefulness-promoting agent modafinil. We suggest that modafinil may reinforce the action of SD, possibly by preventing daytime naps and microsleep, and may sustain the antidepressant effect of SD, possibly by stabilizing the resynchronization between the circadian clock and the sleep-wake cycle.

Aged↗

Prior sleep with zolpidem enhances the effect of caffeine or modafinil during 18 hours continuous work.

INTRODUCTION: Continuous military operations may disrupt sleep-wakefulness cycles, resulting in impaired performance and fatigue. We assessed the treatment efficacy of a hypnotic-psychostimulant combination to maintain sleep quality, performance, and alertness during a 42-h simulated military operation. METHODS: A 6-h prophylactic sleep period with zolpidem (ZOL) followed by a 18-h continuous work period with administration at midway of 300 mg of slow release caffeine (CAF) or 200 mg of modafinil (MOD) was performed by eight healthy male subjects. Performance level was assessed with a reaction time test, a memory search test, a dual task, an attention test, and a computerized Stroop test. Cortical activation level was evaluated by the Critical Flicker Frequency test. Subjective sleepiness was evaluated using a visual analog scale and questionnaires. Effects of drugs on prophylactic and recovery sleep were also quantified from EEG recordings. RESULTS: CAF and MOD maintained performance and alertness throughout the 18-h work period. As shown by EEG recordings, ZOL improved prophylactic sleep without any deleterious effect on performance immediately after waking. As a result of its positive effects on prophylactic sleep, a lower pressure for slow wave sleep during recovery sleep was observed; nevertheless, zolpidem did not enhance the effects of either psychostimulant on performance. DISCUSSION: MOD and CAF may be of value in promoting performance and wakefulness during shiftwork or military operations while zolpidem improves prophylactic sleep quality without any deleterious effect after waking. We concluded that a zolpidem/ caffeine or modafinil combination could be useful in a context of environmental conditions not conducive to sleep.

Adult↗

[Study by EPR of structural modifications on liposomes induced by two metabolites of modafinil].

Awaking properties of modafinil are well known at this time, but its action mode is still hypothetic. Our contribution is limited to the study of the membrane structural modifications carried by this drug and two metabolites. By EPR spectroscopy, we have studied the two metabolites which are distinguished by acid function for the first one and sulfone function for the second one. These two metabolites have no waking properties when they are administrated to animals but one of these two metabolites has the same behaviour than modafinil on membrane action.

Benzhydryl Compounds↗

Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats.

Modafinil (MOD) is a wakefulness-promoting drug that improves the alertness levels in narcolepsy; however, the molecular mechanism of action remains to be elucidated. We found that after a single icv injection of MOD (10 microg/5 microl) the extracellular levels of dopamine (DA) and l-DOPA collected from the nucleus accumbens were increased and decreased, respectively. Separately, the icv administration of MOD (10 microg/5 microl) to rats enhanced wakefulness (W) whereas diminished sleep during 4h. Lastly, the alertness induced by MOD was partially antagonized by the sleep-inducing endocannabinoid anandamide (ANA). We conclude that MOD enhances the extracellular levels of DA, promotes W and its effects on sleep are partially blocked by ANA.

Analysis of Variance↗

High-performance liquid chromatographic determination of modafinil and its two metabolites in human plasma using solid-phase extraction.

A simple procedure for the simultaneous determination of modafinil, its acid and sulfone metabolites in plasma is described. The assay involved an extraction of the drug, metabolites and internal standard from plasma with a solid-phase extraction using C18 cartridges. These compounds were eluted by methanol. The extract was evaporated to dryness at 40 degrees C under a gentle stream of nitrogen. The residue was redissolved in 250 microl of mobile-phase and a 30 microl aliquot was injected via an automatic sampler into the liquid chromatograph and eluted with the mobile-phase (26%, v/v acetonitrile in 0.05 M orthophosphoric acid buffer adjusted to pH 2.6) at a flow-rate of 1.1 ml/min on a C8 Symmetry cartridge column (5 microm, 150 mm x 3.9 mm, Waters) at 25 degrees C. The eluate was detected at 225 nm. Intra-day coefficients of variation ranged from 1.0 to 2.9% and inter-day coefficients from 0.9 to 6.1%. The limits of detection and quantitation of the assay were 0.01 microg/ml and 0.10 microg/ml respectively.

Administration, Oral↗

Modafinil in sports: ethical considerations.

Performance enhancing agents are prohibited in athletic competition so that only athletic skills can determine outcomes. Modafinil is a novel non-addicting psychostimulant approved for treatment of narcolepsy. Does its use, especially for medical indications, violate the Olympic Movement Anti-Doping Code? This is discussed with reference to a current high profile case.

Benzhydryl Compounds↗

Modafinil augmentation of mirtazapine in a failure-to-thrive geriatric inpatient.

The failure-to-thrive syndrome in geriatric patients is marked by social withdrawal, apathy, depression, anorexia, and cognitive impairment. For therapy to be effective, the treatment plan must target several of theseareas. This case report describes one such course of treatment for a patient with multiple myeloma with failure-to-thrive who was successfully treated with modafinil and mirtazapine. By using combination pharmacotherapy, we were able to achieve immediate results in a gravely ill patient.

Aged↗

Methylphenidate and narcolepsy: new indication. When modafinil fails.

(1) Narcolepsy (daytime bouts of drowsiness) is sometimes associated with cataplexy, and can be incapacitating. The best-assessed treatment is modafinil, which has no demonstrated efficacy on cataplexy. (2) After many years of off-license use in the treatment of narcolepsy, methylphenidate is now licensed for this indication in France. (3) According to the results of our literature search, which includes a clinical expert report from Novartis Pharma, the file on methylphenidate in narcolepsy is mainly based on "clinical experience": only three case series, totalling fewer than 200 patients, have been published. (4) These non comparative studies suggest an effect of high dose methylphenidate on daytime drowsiness and cataplexy. (5) The adverse effects of methylphenidate are those of amphetamine psychostimulants, i.e. mainly neuropsychological disorders, cardiovascular effects, loss of appetite and a limited risk of excessive use by some patients.

Benzhydryl Compounds↗