Armodafinil

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Summary sheet: Armodafinil
Armodafinil
Armodafinil.svg
Chemical Nomenclature
Common names Armodafinil, Nuvigil, Waklert, Artvigil, R-Modawake, Neoresotyl
Substitutive name (R)-Modafinil
Systematic name 2-[(R)-benzhydrylsulfinyl]acetamide
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold 20 - 40 mg
Light 40 - 100 mg
Common 100 - 200 mg
Strong 200 - 300 mg
Heavy 300 mg +
Duration
Total 8 - 15 hours
Onset 20 - 60 minutes
Come up 1 - 2.5 hours
Peak 4 - 7 hours
Offset 2 - 5 hours
After effects 2 - 12 hours









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

(R)-Modafinil (commonly known as Armodafinil and by the brand names Artvigil and Waklert[1]) is the enantiopure formulation of modafinil (brand name Provigil). As opposed to the racemic formulation, which contains a 50/50 mix of both the (S) and (R) enantiomers, armodafinil consists of just the (R)-enantiomer of modafinil, which is a synthetic nootropic and eugeroic (i.e. wakefulness-promoting agent) of the benzhydryl chemical class.

Armodafinil was approved by the U.S. Food and Drug Administration (FDA) in June 2007 for the treatment of obstructive sleep apnea, shift work sleep disorder, and narcolepsy.[2]

In addition to its wakefulness-promoting effects and ability to increase locomotor activity in animals, armodafinil can produce rewarding psychoactive and euphoric effects such as alterations in mood, perception, thinking, and feelings typically observed with other central nervous system (CNS) stimulants in humans.

A study in which patients were administered modafinil, methylphenidate, and a placebo found that modafinil produces "psychoactive and euphoric effects and feelings consistent with methylphenidate."[3] Relative to modafinil, armodafinil reaches its peak concentration in the blood later after administration than modafinil does, which may make it more effective at improving wakefulness in patients with excessive daytime sleepiness.[citation needed]

It should be noted that this compound is a commonly prescribed prescription medication, thus it is considerably less likely to have unforeseen adverse health effects than that of a novel research chemical. Nevertheless, the long-term risks of regular armodafinil intake have yet to be studied in detail.[citation needed]

Chemistry

(R)-Modafinil, or Armodafinil, is a psychoactive molecule of the benzhydryl class. Benzhydryl compounds are comprised of two benzene rings attached to a single carbon molecule. Armodafinil is classified as a sulphinyl benzhydryl molecule, as it also contains a sulphinyl group, a sulfur molecule double-bonded to an oxygen molecule attached to the carbon of the benzhydryl group.

From this sulfur group at R2, an acetamide group is bound at its free carbon through a carbonyl group to a terminal amine group. Armodafinil has a center of chirality at its sulfur group. Armodafinil, unlike modafinil, consists of only the (−)-(R)-enantiomer of modafinil.

Pharmacology

(R,S)-modafinil, mechanism of action.

Although the exact mechanisms by which modafinil and its R-enantiomer, armodafinil, decrease sleepiness are not fully understood, evidence suggests that these agents promote wakefulness by acting directly or indirectly on many components of the sleep / wake circuit. Modafinil and armodafinil are hypothesized to inhibit GABA and promote dopamine, norepinephrine, histamine, and hypocretin / orexin.[4][5][6][7]

Modafinil and its R-enantiomer, armodafinil, increase both norepinephrine (NE) and dopamine (DA), possibly via their blockade of both the NE and DA reuptake transporters (NET and DAT, respectively). The actions of NE at alpha-adrenergic receptors and DA at dopamine D2 receptors are thought to contribute to the wake-promoting properties of modafinil. Orexin is a key component of the arousal system; thus, the hypothesized action of modafinil on the orexinergic system may help increase alertness. Additionally, modafinil may indirectly increase histamine, either by reducing GABAergic inhibition of histaminergic neurons or via actions at orexinergic neurons. The increase in histamine may contribute to both the wake-promoting effects of modafinil as well as the potential of modafinil to increase alertness.[4][6][8]

In genetically engineered mice lacking the dopamine transporter (DAT), modafinil lacked wake-promoting activity, suggesting that this activity was DAT-dependent. However, the wake-promoting effects of modafinil, unlike those of amphetamine, were not reduced by the dopamine receptor antagonist haloperidol in rats. In addition, alpha-methyl-p-tyrosine, an inhibitor of dopamine synthesis, blocks the action of amphetamine but does not block locomotor activity induced by modafinil.

Subjective effects

In comparison to traditional stimulants such as amphetamine, this compound induces an experience which is far less forceful, recreational and euphoric. It instead focuses on general wakefulness and motivation enhancement. In comparison to regular modafinil it is usually considered to be less side effect intensive, more comfortable and with a longer duration.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
Child.svg


Toxicity and harm potential

The long-term safety and effectiveness of Armodafinil as a drug of regular usage have not been determined.[15] Anecdotal evidence from experience reports suggest a lack of adverse health effects when sparingly used at small to moderate doses, although this must not be assumed.

This compound is a commonly prescribed prescription medication, thus is considerably less likely to have adverse health effects than that of a typical research chemical.

It is strongly recommended that one use harm reduction practices when using this drug.

Lethal dosage

The median lethal dose at which 50% of participants die (LD50) from either armodafinil or modafinil for human beings has never been reached. No life-threatening effects have taken place in clinical trials involving the administration of 1000mg to 1600mg of modafinil per day for 7 to 21 consecutive days. Intentional acute overdoses of 4500mg and 4000mg in two adult subjects and an accidental ingestion of 800mg by a three-year-old child did not result in any life-threatening effects or death.[16] After overdosing on 5000mg of modafinil in a suicide attempt, a fifteen-year-old female reported a severe headache, nausea, and tachycardia, but did not appear to have any lethal or long-term effects.[17]

Tolerance and addiction potential

Armodafinil, like racemic modafinil, may also possess addiction reinforcing properties, as evidenced by its self-administration in monkeys previously trained to administer cocaine; armodafinil was also partially discriminated as stimulant-like. The chronic use of armodafinil can be considered as mildly addictive with a low potential for abuse. It does not seem to be capable of causing psychological dependence among certain users.

Tolerance to many of the effects of armodafinil develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Armodafinil may present a cross-tolerance with all benzhydryl nootropics, meaning that after the consumption of modafanil certain nootropics such as modafanil and adrafanil may have a reduced effect.

Dangerous interactions

Although many psychoactive substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

Legal status

Armodafinil is legally approved for medical purposes worldwide. However, it is illegal to sell and possess in most countries without a prescription.

  • United States - In the United States, armodafinil is a Schedule IV controlled substance. It is illegal to buy, sell, or possess the drug without a prescription or DEA license.[21]
  • Canada - Modafinil is listed as a Schedule F prescription drug in Canada and it can be prescribed for human and veterinary use.[22]
  • United Kingdom - This substance is not a licensed medicine in the United Kingdom and is not covered by the Misuse of Drugs Act 1971 so it may be considered illegal to produce, supply, or import under the Psychoactive Substances Act.[23] However, it may not be covered by the Psychoactive Substances Act as it is a licensed medicine in many other countries[citation needed] and modafinil, the non-enantiopure substance that is comprised of armodafinil and the S-enantiomer of modafinil in equal proportions, is a licensed prescription-only medicine (POM) in the United Kingdom.[24] In this case it would not be considered a criminal offence to possess this substance without a valid prescription and it could be legally be obtained with a valid prescription or through legal import of the substance for personal use as outlined in Section 13 of the Medicines Act 1968.[25]

See also

External links

Literature

  • Bello, N. T. (2015). Central Nervous System Stimulants and Drugs That Suppress Appetite. In Side Effects of Drugs Annual (Vol. 37, pp. 1–13). Elsevier. https://doi.org/10.1016/bs.seda.2015.08.004
  • Conrado, D. J., Bewernitz, M., Ding, M., Cibula, J., Seubert, C., Sy, S. K. B., … Derendorf, H. (2013). Electroencephalogram effects of armodafinil: Comparison with behavioral alertness. The Journal of Clinical Pharmacology, 53(10), 1058–1071. https://doi.org/10.1002/jcph.143
  • Darwish, M., Kirby, M., D’Andrea, D. M., Yang, R., Hellriegel, E. T., & Robertson, P. (2010). Pharmacokinetics of armodafinil and modafinil after single and multiple doses in patients with excessive sleepiness associated with treated obstructive sleep apnea: A randomized, open-label, crossover study. Clinical Therapeutics, 32(12), 2074–2087. https://doi.org/10.1016/j.clinthera.2010.11.009
  • Fuller, P., Vetrivelan, R., & Saper, C. (2014). Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions. Nature and Science of Sleep, 6, 57. https://doi.org/10.2147/NSS.S53132
  • Greve, D. N., Duntley, S. P., Larson-Prior, L., Krystal, A. D., Diaz, M. T., Drummond, S. P. A., … Thomas, R. J. (2014). Effect of Armodafinil on Cortical Activity and Working Memory in Patients with Residual Excessive Sleepiness Associated with CPAP-Treated OSA: A Multicenter fMRI Study. Journal of Clinical Sleep Medicine, 10(2), 143–153. https://doi.org/10.5664/jcsm.3440
  • Kaye, A. M., & Urman, R. D. (2015). Essentials of Pharmacology for Anesthesia, Pain Medicine, and Critical Care. (A. D. Kaye, A. M. Kaye, & R. D. Urman, Eds.). New York, NY: Springer New York. https://doi.org/10.1007/978-1-4614-8948-1
  • Loland, C. J., Mereu, M., Okunola, O. M., Cao, J., Prisinzano, T. E., Mazier, S., … Newman, A. H. (2012). R-modafinil (armodafinil): A unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biological Psychiatry, 72(5), 405–413. https://doi.org/10.1016/j.biopsych.2012.03.022
  • Morrissette, D. A. (2013). Twisting the night away: a review of the neurobiology, genetics, diagnosis, and treatment of shift work disorder. CNS Spectrums, 18(s1), 42–54. https://doi.org/10.1017/S109285291300076X
  • Nevsimalova, S. (2014). The diagnosis and treatment of pediatric narcolepsy. Current Neurology and Neuroscience Reports, 14(8). https://doi.org/10.1007/s11910-014-0469-1
  • Niemegeers, P., Maudens, K. E., Morrens, M., Patteet, L., Joos, L., Neels, H., & Sabbe, B. G. (2012). Pharmacokinetic evaluation of armodafinil for the treatment of bipolar depression. Expert Opinion on Drug Metabolism & Toxicology, 8(9), 1189–1197. https://doi.org/10.1517/17425255.2012.708338
  • Ramachandra, B. (2016). A Critical Review of Properties of Modafinil and Analytical, Bioanalytical Methods for its Determination. Critical Reviews in Analytical Chemistry, 46(6), 482–489. https://doi.org/10.1080/10408347.2016.1153948
  • Rosenberg, R. P., Bogan, R. K., Tiller, J. M., Yang, R., Youakim, J. M., Earl, C. Q., & Roth, T. (2010). A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Armodafinil for Excessive Sleepiness Associated With Jet Lag Disorder. Mayo Clinic Proceedings, 85(7), 630–638. https://doi.org/10.4065/mcp.2009.0778
  • T., M., M., M., N., S., & S., N. (2016). The pathogenesis of narcolepsy, current treatments, and prospective therapeutic targets. Expert Opinion on Orphan Drugs, 4(1), 63–82. https://doi.org/10.1517/21678707.2016.1117973
  • Wright, K. P., Bogan, R. K., & Wyatt, J. K. (2013). Shift work and the assessment and management of shift work disorder (SWD). Sleep Medicine Reviews, 17(1), 41–54. https://doi.org/10.1016/j.smrv.2012.02.002
  • Zee, P. C., Attarian, H., & Videnovic, A. (2013). Circadian Rhythm Abnormalities. CONTINUUM Lifelong Learning in Neurology, 19(February), 132–147. https://doi.org/10.1212/01.CON.0000427209.21177.aa

References

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  16. The National Library of Medicine - PROVIGIL | http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fd75a8a7-a8ab-4141-9af9-989a220b9c19
  17. Journal of Clinical Sleep Medicine - Unsuccessful Suicide Attempt of a 15 Year Old Adolescent with Ingestion of 5000 mg Modafinilhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725258
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