How does Armodafinil act as a Wakefulness agent?

Are you working night shifts and facing difficulties sleeping during day time? Do your work hours overlap with typical sleep time? Because of this you are lacking concentration? Modern-day advancements in medical sciences have found solutions although not for all, but most human diseases and illnesses.

Everyone now recognizes psychological disorders and mental illnesses and there is treatment as well. The answer to your worries may a nootropic that help you to enhance your cognitive function as well as improve memory. One such psychostimulant is Armodafinil that can help you remain wakeful and aid in fighting sleeping disorders (1,2).

What is Armodafinil?

You all must have heard of the famous smart drug modafinil drug. Armodafinil is quite similar to it but still, both are not the same. Modafinil contains a mixture of molecules that have mirrored chemical structure known as the racemic mixture. Think of them like the gloves of right and left hands. So, R- and S- enantiomers, as they are called, present in modafinil. Armodafinil only contains R-enantiomer (3).

How does it help?

Like modafinil, not much is clear about how armodafinil works. But it appears that armodafinil produces its effects in indirect ways. Armodafinil seems to act on the receptors responsible for the reuptake of dopamine. When these receptors are blocked, the concentration of dopamine increases in some areas of the brain. Although the exact mechanism is not known, armodafinil is believed to increase the concentration of certain neurotransmitters like norepinephrine, orexin, serotonin, and histamine. Armodafinil does not bind or inhibit any of the receptors directly (4).

What makes Armodafinil better?

As proved by researches, Armodafinil promotes wakefulness, helps to get you better cognitive function, increases alertness and memory, and improves mood. It results in efficient productivity and is used as a complementary therapy for depression (5–8).

Who can use it?

Armodafinil is a wakefulness-promoting agent usually prescribed to individuals facing extreme sleepiness due to any sleep disorder. Although armodafinil does not itself treats the sleeping disorder but promotes functionality and wakefulness during the day. People with the following conditions benefit from Armodafinil.

1. Narcolepsy: A sleep disorder in which a person falls asleep if they find a situation or position relaxing. Thus, such individuals can sleep anywhere and at any time of the day. Although many drugs have been developed to fight this sleeping disorder, Armodafinil is the most effective one. It helps fight excessive sleepiness during the daytime and allows active participation in different functions throughout the day without the person falling asleep (9).

2. Obstructive sleep apnea (OSP): It is a sleep- relate breathing disorder in which the breathing stops for a brief time during sleep leading the person to wake up again and again. This results in excessive sleepiness during the daytime. Armodafinil helps to overcome this excessive sleepiness during the day (10).

3. Shift-work Disorder (SWD): It is a sleeping disorder often face by individuals who work night shifts or long and irregular hours. Such individuals often experience extreme sleepiness during work hours and when they get time to sleep during the day, they have difficulty in falling asleep. Armodafinil helps individuals with SWD to retain attention and remain active and awake during work hours (11).

How Armodafinil is better than Modafinil?

Although both have similar chemical structures and promote wakefulness, still armodafinil is a better choice. Armodafinil has a half-life of 15 hours which is three times longer than modafinil having a half-life of 3 to 4 hours (12). When both are administered in the same quantity, the concentration of armodafinil in the plasma remains maintained longer than modafinil i.e., 14-16 hours after administration resulting in better wakefulness than modafinil (13). 150 mg of armodafinil produces the same effect as 200mg of modafinil making armodafinil more potent (11).

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Sources

1. Garnock-Jones KP, Dhillon S, Scott LJ. Armodafinil. CNS Drugs. 2009 Sep 1;23(9):793–803.
2. Hirshkowitz M, Black JE, Wesnes K, Niebler G, Arora S, Roth T. Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome. Respir Med. 2007 Mar;101(3):616–27.
3. Loland CJ, Mereu M, Okunola OM, Cao J, Prisinzano TE, Mazier S, et al. R-Modafinil (Armodafinil): A Unique Dopamine Uptake Inhibitor and Potential Medication for Psychostimulant Abuse. Biological Psychiatry. 2012 Sep 1;72(5):405–13.
4. Lankford DA. Armodafinil: a new treatment for excessive sleepiness. Expert Opinion on Investigational Drugs. 2008 Apr 1;17(4):565–73.
5. Czeisler CA, Walsh JK, Wesnes KA, Arora S, Roth T. Armodafinil for Treatment of Excessive Sleepiness Associated With Shift Work Disorder: A Randomized Controlled Study. Mayo Clin Proc. 2009 Nov;84(11):958–72.
6. Harsh JR, Hayduk R, Rosenberg R, Wesnes KA, Walsh JK, Arora S, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Current Medical Research and Opinion. 2006 Apr 1;22(4):761–74.
7. Lower EE, Malhotra A, Surdulescu V, Baughman RP. Armodafinil for Sarcoidosis-Associated Fatigue: A Double-Blind, Placebo-Controlled, Crossover Trial. Journal of Pain and Symptom Management. 2013 Feb 1;45(2):159–69.
8. Calabrese JR, Ketter TA, Youakim JM, Tiller JM, Yang R, Frye MA. Adjunctive Armodafinil for Major Depressive Episodes Associated With Bipolar I Disorder: A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Proof-of-Concept Study. J Clin Psychiatry. 2010 Jul 27;71(10):0–0.
9. Scammell TE. Narcolepsy. New England Journal of Medicine. 2015 Dec 31;373(27):2654–62.
10. Kuan YC, Wu D, Huang K-W, Chi N-F, Chung C-C, Hu C-J, et al. Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials. Clinical therapeutics [Internet]. 2016 Apr [cited 2021 May 22];38(4).
11. Tembe DV, Dhavale A, Desai H, Mane DN, Raut SK, Dhingra G, et al. Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial. Neurology Research International. 2011 Jun 1;2011:e514351.
12. Guilleminault C, Cao MT. Chapter 85 - Narcolepsy: Diagnosis and Management. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine (Fifth Edition) [Internet]. Philadelphia: W.B. Saunders; 2011 [cited 2021 May 22]. p. 957–68.