Modafinil

Modafinil is a prescription medicine for narcoleptics that increases alertness and prevents sleep. It just so happens to also increase cognition and memory, and is a potent and highly regarded supplement in the category of nootropics

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Modafinil is an awakefulness enchancing drug that was created for treatment of daytime sleep related disorders such as Narcolepsy. It seems to have benefits for cognition via increasing levels of stimulatory neurotransmitters in the brain, and is used recreationally as a smart-drug.

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Also Known As

2-[(Diphenylmethyl) sulfinyl]acetamide, Provigil, Modalert, Modapro, Alertex


Do Not Confuse With

Adrafinil


Things to Note

  • At least in the US and Canada, Modafinil is labeled a prescription drug and may not be easily acquirable. It is a Schedule IV controlled substance in the US.

Is a Form of


Caution Notice

Examine.com Medical Disclaimer

Standard dosages are 100-200mg, or perhaps 4mg/kg bodyweight, taken in a sleep-deprived state for best effects.


Table of Contents:


Edit1. Structure and Sources

Modafinil is a pharmaceutical designed for usage in sleep-related disorders, and is related to improved mental function in a sleep deprived state.[1]


Edit2. Mechanisms of action (General)

2.1. Sleep/Wake cycles

The sleep wake cycle of the brain is a balance of the 'ascending arousal system' consisting of arousing neurotransmitters (catecholamines, acetylcholine, orexin, etc.) and the neurotransmitters (GABA, Galanin) which act to suppress stimulation and promote sleep.[2][3] Varying levels of arousing and depressing neurotransmitters form an 'on-off' switch for arousal and sleep.[1]

Overall regulation of the wakefulness and rest cycle seems to be in part due to the circadian rhythm, mediated by the Suprachiasmatic Nuclei (SCN), and in part due to homeostatic needs for sleep that are gained during wakefulness.[2][3]


Edit3. Neuronal Mechanisms of action

Modafinil seems to be able to interact with a multitude of stimulatory systems including serotonergic, noradrenergic, dopaminergic, glutaminergic, histaminergic, and orexinergic pathways; and also influences GABAergic pathways.[4]

3.1. Dopaminergic interactions

Modafinil seems to be able to increase extracellular levels of dopamine in the rat nucelar accumbens[5] and prefrontal cortex[6] and the dog caudate nucleus.[7] It has been shown to occupy both the dopamine and noradrenaline receptors (in the striatum)[8] and prevention of dopamine receptor occupancy abolishes the sleep-promoting effects in mice[9], suggesting this mechanism of action is crucial to the sleep-promoting effects.[10]dopamine release and alters the subjective properties of stimulants|published=2007 Jul 30|authors=Dopheide MM, Morgan RE, Rodvelt KR, Schachtman TR, Miller DK|journal=Eur J Pharmacol]dopamine release and alters the subjective properties of stimulants]

Past studies have noted a lack of potency of modafinil on dopaminergic systems[11][12][13] which may be due to the lower dosages they used in those studies relative to more recent ones.

3.2. Adrenergic interactions

3.3. Serotonergic interactions

3.4. Orexinergic interactions

In those with faulty orexin levels (narcoleptics)[14], modafinil shows benefit possibly by acting on orexic neurons directly.[15][16] This effect is more potent in orexin-knockout mice than in normal mice[17], and the effects of modafinil on the orexin system of healthy persons is unknown.[1]


Edit4. In vivo Trials

4.1. Humans

Modafinil has been found in healthy persons to aid in cognitive function in a fatigued state (after a shift of work).[18]

Modafinil seems to disrupt the ability of one to voluntarily fall asleep.[18]

4.2. Laboratory animals

References

  1. Approved and Investigational Uses of Modafinil: An Evidence-Based Review
  2. Hypothalamic regulation of sleep and circadian rhythms
  3. Neurobiology of the Sleep-Wake Cycle: Sleep Architecture, Circadian Regulation, and Regulatory Feedback
  4. Modafinil: A Review of Neurochemical Actions and Effects on Cognition
  5. Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats
  6. de Saint Hilaire Z, et al. Variations in extracellular monoamines in the prefrontal cortex and medial hypothalamus after modafinil administration: a microdialysis study in rats. Neuroreport. (2001)
  7. Dopaminergic Role in Stimulant-Induced Wakefulness
  8. Madras BK, et al. Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro. J Pharmacol Exp Ther. (2006)
  9. Modafinil inhibits rat midbrain dopaminergic neurons through D2-like receptors
  10. Modafinil evokes striatal [(3)H
  11. Lack of pre-synaptic dopaminergic involvement in modafinil activity in anaesthetized mice: In vivo voltammetry studies
  12. Mignot E, et al. Modafinil binds to the dopamine uptake carrier site with low affinity. Sleep. (1994)
  13. Akaoka H, et al. Effect of modafinil and amphetamine on the rat catecholaminergic neuron activity. Neurosci Lett. (1991)
  14. The hypocretin/orexin system in health and disease
  15. Chemelli RM, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. (1999)
  16. Hypothalamic Arousal Regions Are Activated during ModafinilInduced Wakefulness
  17. Modafinil more effectively induces wakefulness in orexin-null mice than in wild-type littermates
  18. Gill M, et al. Cognitive performance following modafinil versus placebo in sleep-deprived emergency physicians: a double-blind randomized crossover study. Acad Emerg Med. (2006)

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