An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil

Murillo-Rodrı́guez, Eric; Veras, André Barciela; Rocha, Nuno; Budde, Henning; Machado, Sérgio

doi:10.1021/acschemneuro.7b00374

Cited by 73 publications

(58 citation statements)

References 112 publications

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“…Sulfoxides with electrondonating or electron-withdrawing groups at the aryl moiety (3 a-d) were obtained (entries 2-4), but longer reaction times were needed for electron-deficient aryl groups. [56] We were pleased to isolate the corresponding sulfoxide 3 i (modafinil) in 75 % yield, using the mild and environmentally-friendly oxidation protocol developed. [55] Interestingly, dialkyl sulfides (entries 7 and 8), including the sterically hindered tert-butylmethyl derivative (2 g), were efficiently oxidized to 3 g-h in shorter reaction times (entries [8][9].…”

Section: Full Papersmentioning

confidence: 99%

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Imine‐Based Covalent Organic Frameworks as Photocatalysts for Metal Free Oxidation Processes under Visible Light Conditions

et al. 2019

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Photochemistry of extended polyimine COF structures with laminar, spherical and 3D architectures has been examined. We show that these materials, composed by undecorated phenyl rings and imine fragments, can act as photocatalyts in oxidative transformations, being the crystalline laminar material the most active photocatalyst. The sulfoxidation reaction proceeds with good yields for a large variety of different sulfides. This process was carried out under visible light conditions (20 W), ethanol/ H 2 O as solvent, and the heterogeneous porous material can be recycled up to 9 times. The crystallinity favours the behavior as photocatalyst of laminar and spherical COFs whereas any particular effect on the 3D material activity was observed. Sulfoxidation reaction mainly proceeds through an energy transfer mechanism using crystalline laminar material. In addition, these materials as photocatalysts were used for the oxidation of phenyl boronic acid into phenol. . a) Catalytic runs in the oxidation of sulfide 2 a to 3 a in nine consecutive 24 hours catalytic runs by addition of 0.3 mmol of sulfide 2 a after each cycle (see S.I. for further information). The output of the catalytic reaction is expressed as mmol of 3 a generated per cycle. Characterization after one catalytic cycle: b) SEM image of crystalline Laminar-COF 1 b c) FT-IR (black colour before catalysis and red colour after catalysis) d) PXRD (black colour before catalysis, red colour, after catalysis). Scheme 1. Mechanistic plausible scenarios for photocatalytic aerobic sulfoxidation reactions (PC = photocatalyst).

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Section: Full Papersmentioning

confidence: 99%

“…Moreover, the effectiveness of the crystalline material 1 b was evaluated in the oxidation of sulfide 2 i, which is known to be the precursor of the drug modafinil. [56] We were pleased to isolate the corresponding sulfoxide 3 i (modafinil) in 75 % yield, using the mild and environmentally-friendly oxidation protocol developed.…”

Section: Full Papersmentioning

confidence: 99%

Imine‐Based Covalent Organic Frameworks as Photocatalysts for Metal Free Oxidation Processes under Visible Light Conditions

et al. 2019

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“…Similarly, an ␣1-AR antagonist blocks the improvement in executive function induced by modafinil in healthy human subjects (Winder-Rhodes et al, 2010). Modafinil is used to treat narcolepsy and fatigue (Murillo-Rodríguez et al, 2018). Therefore, boosting ␣1-AR actions may help subjects with insufficient, endogenous NE actions.…”

Section: Clinical Relevancementioning

confidence: 99%

Noradrenergic α1-Adrenoceptor Actions in the Primate Dorsolateral Prefrontal Cortex

et al. 2019

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Noradrenergic (NE) ␣1-adrenoceptors (␣1-ARs) contribute to arousal mechanisms and play an important role in therapeutic medications such as those for the treatment of posttraumatic stress disorder (PTSD). However, little is known about how ␣1-AR stimulation influences neuronal firing in the dorsolateral prefrontal cortex (dlPFC), a newly evolved region that is dysfunctional in PTSD and other mental illnesses. The current study examined the effects of ␣1-AR manipulation on neuronal firing in dlPFC of rhesus monkeys performing a visuospatial working memory task, focusing on the "delay cells" that maintain spatially tuned information across the delay period. Iontophoresis of the ␣1-AR antagonist HEAT (2-{[␤-(4-hydroxyphenyl)ethyl]aminomethyl}-1-tetralone) had mixed effects, reducingfiring in a majority of neurons but having nonsignificant excitatory effects or no effect in remaining delay cells. These data suggest that endogenous NE has excitatory effects in some delay cells under basal conditions. In contrast, the ␣1-AR agonists phenylephrine and cirazoline suppressed delay cell firing and this was blocked by coadministration of HEAT. These results indicate an inverted-U dose response for ␣1-AR actions, with mixed excitatory actions under basal conditions and suppressed firing with high levels of ␣1-AR stimulation such as with stress exposure. Immunoelectron microscopy revealed ␣1-AR expression presynaptically in axons and axon terminals and postsynaptically in spines, dendrites, and astrocytes. It is possible that ␣1-AR excitatory effects arise from presynaptic excitation of glutamate release, whereas postsynaptic actions suppress firing through calcium-protein kinase C opening of potassium channels on spines. The latter may predominate under stressful conditions, leading to loss of dlPFC regulation during uncontrollable stress. Significance StatementNoradrenergic stimulation of ␣1-adrenoceptors (␣1-ARs) is implicated in posttraumatic stress disorder (PTSD) and other mental disorders that involve dysfunction of the prefrontal cortex, a brain region that provides top-down control. However, the location and contribution of ␣1-ARs to prefrontal cortical physiology in primates has received little attention. This study found that ␣1-ARs are located near prefrontal synapses and that ␣1-AR stimulation has mixed effects under basal conditions. However, high levels of ␣1-AR stimulation, as occur with stress, suppress neuronal firing. These findings help to explain why we lose top-down control under conditions of uncontrollable stress when there are high levels of noradrenergic release in brain and why blocking ␣1-AR, such as with prazosin, may be helpful in the treatment of PTSD.

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“…3a). In R6/2 mice at 12 weeks, only the beta power at frequencies of [25][26][27][28][29][30] Hz increased in response to modafinil, whilst in R6/2 mice at 16 weeks, only the power of 29-30 Hz increased (Fig. 3b, c).…”

Section: Acute Modafinil Reduces Power Of Slow But Increases Power Omentioning

confidence: 91%

“…Alpha (10-14 Hz) power was reduced in WT and R6/2 mice at 16 weeks, but not in R6/2 mice at 12 weeks. For beta (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) power, the effect varied across the frequency range. For WT mice, the power at frequencies < 20 Hz decreased significantly, whilst power at frequencies > 29 Hz increased significantly (Fig.…”

Section: Acute Modafinil Reduces Power Of Slow But Increases Power Omentioning

confidence: 95%

Wake-Promoting and EEG Spectral Effects of Modafinil After Acute or Chronic Administration in the R6/2 Mouse Model of Huntington's Disease

et al. 2020

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Huntington's disease (HD) is characterised by progressive symptoms including cognitive deficits and sleep/wake disturbances reflected in an abnormal electroencephalography (EEG). Modafinil, a wake-promoting and cognitive-enhancing drug, has been considered as a treatment for HD. We used HD (R6/2) mice to investigate the potential for using modafinil to treat sleep-wake disturbance in HD. R6/2 mice show sleep-wake and EEG changes similar to those seen in HD patients, with increased rapid eye movement sleep (REMS), decreased wakefulness/increased non-REMS (NREMS), and pathological changes in EEG spectra, particularly an increase in gamma power. We recorded EEG from R6/2 and wild-type mice treated with modafinil acutely (with single doses between 25 and 100 mg/kg; at 12 and 16 weeks of age), or chronically (64 mg/kg modafinil/day from 6 to 15 weeks). Acutely, modafinil increased wakefulness in R6/2 mice and restored NREMS to wild-type levels at 12 weeks. It also suppressed the pathologically increased REMS. This was accompanied by decreased delta power, increased peak frequency of theta, and increased gamma power. At 16 weeks, acute modafinil also restored wakefulness and NREMS to wild-type levels. However, whilst REMS decreased, it did not return to normal levels. By contrast, in the chronic treatment group, modafinil-induced wakefulness was maintained at 15 weeks (after 9 weeks of treatment). Interestingly, chronic modafinil also caused widespread suppression of power across the EEG spectra, including a reduction in gamma that increases pathologically in R6/2 mice. The complex EEG effects of modafinil in R6/2 mice should provide a baseline for further studies to investigate the translatability of these result to clinical practice.

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An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil

Cited by 73 publications

References 112 publications

Imine‐Based Covalent Organic Frameworks as Photocatalysts for Metal Free Oxidation Processes under Visible Light Conditions

Imine‐Based Covalent Organic Frameworks as Photocatalysts for Metal Free Oxidation Processes under Visible Light Conditions

Noradrenergic α1-Adrenoceptor Actions in the Primate Dorsolateral Prefrontal Cortex

Wake-Promoting and EEG Spectral Effects of Modafinil After Acute or Chronic Administration in the R6/2 Mouse Model of Huntington's Disease

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