Eugeroics (originally "eugrégorique" or "eugregoric"), also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...

s that promote

wakefulness Wakefulness is a daily recurring brain state and state of consciousness in which an individual is conscious and engages in coherent cognitive and behavioral responses to the external world. Being awake is the opposite of being asleep, in which m ...

and

alertness Alertness is the state of active attention by high sensory awareness such as being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related for psychology . A lack of alertness is a symptom of a n ...

. They are medically indicated for the treatment of certain

sleep disorder A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Polysomnography and actigraphy are tes ...

s including excessive daytime sleepiness (EDS) in

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...

or obstructive sleep apnea (OSA). Eugeroics are also often prescribed

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although mo ...

for the treatment of EDS in

idiopathic hypersomnia Idiopathic hypersomnia (IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). The condition typically becomes evident in early adulthood and most patients diagnosed with IH will ...

, a rare and often debilitating sleep disorder which currently has no official treatments approved by the

Food and Drug Administration (FDA) Food is any substance consumed by an organism for Nutrient, nutritional support. Food is usually of plant, animal, or Fungus, fungal origin, and contains essential nutrients, such as carbohydrates, fats, protein (nutrient), proteins, vitamins ...

. In contrast to classical

psychostimulants Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

, such as

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...

and

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

, which are also used in the treatment of these disorders, eugeroics typically do not produce

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and dan ...

, and, consequently, have a lower addictive potential.

Modafinil Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant medication used to treat sleepiness due to narcolepsy, shift work sleep disorder, and obstructive sleep apnea. While it has seen off-label ...

and

armodafinil Armodafinil (trade name Nuvigil) is the enantiopure compound of the eugeroic modafinil (Provigil). It consists of only the (''R'')-(−)-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc ...

are each thought to act as selective, weak, atypical dopamine reuptake inhibitors (DRI), whereas

adrafinil Adrafinil, sold under the brand name Olmifon, is a wakefulness-promoting medication that was formerly used in France to improve alertness, attention, wakefulness, and mood, particularly in the elderly. It was also used off-label by individuals w ...

acts as a prodrug for modafinil. Other eugeroics include

solriamfetol Solriamfetol, sold under the brand name Sunosi, is a wakefulness-promoting medication used in the treatment of excessive sleepiness related to narcolepsy and sleep apnea. It is taken by mouth. Common side effects of solriamfetol include h ...

, which acts as a norepinephrine–dopamine reuptake inhibitor (NDRI), and

pitolisant Pitolisant, sold under the brand name Wakix among others, is a medication for the treatment of excessive daytime sleepiness in adults with narcolepsy. It is a histamine 3 (H3) receptor antagonist/inverse agonist. It represents the first commercia ...

, which acts as a histamine 3 (H₃) receptor antagonist/

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse ag ...

Examples

Marketed

Armodafinil Armodafinil (trade name Nuvigil) is the enantiopure compound of the eugeroic modafinil (Provigil). It consists of only the (''R'')-(−)-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc ...

(Nuvigil) *

(Provigil) *

Pitolisant Pitolisant, sold under the brand name Wakix among others, is a medication for the treatment of excessive daytime sleepiness in adults with narcolepsy. It is a histamine 3 (H3) receptor antagonist/inverse agonist. It represents the first commercia ...

(Wakix) *

Solriamfetol Solriamfetol, sold under the brand name Sunosi, is a wakefulness-promoting medication used in the treatment of excessive sleepiness related to narcolepsy and sleep apnea. It is taken by mouth. Common side effects of solriamfetol include h ...

(Sunosi)

Discontinued

Adrafinil Adrafinil, sold under the brand name Olmifon, is a wakefulness-promoting medication that was formerly used in France to improve alertness, attention, wakefulness, and mood, particularly in the elderly. It was also used off-label by individuals w ...

Never marketed

* Flmodafinil (CRL-40,940) * Fluorafinil (CRL-40,941) *

Fluorenol Fluorenol, also known as hydrafinil, is an alcohol derivative of fluorene. In the most significant isomer, fluoren-9-ol or 9-hydroxyfluorene, the hydroxy group is located on the bridging carbon between the two benzene rings. Hydroxyfluorene can b ...

* Methylbisfluoromodafinil *

2-Phenyl-3-aminobutane 2-Phenyl-3-aminobutane (also known as β-methylamphetamine) is a stimulant of the phenethylamine class that is closely related to its α-methyl analog Pentorex. It was first synthesized by the German scientists Felix Haffner and Fritz Sommer in ...

In development

* Selective

orexin receptor The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (, ). Both orexin receptors exhibit ...

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

s (two are currently under development by

Takeda is a Japanese family name.1990 Census Name Files

danavorexton Danavorexton (developmental code name TAK-925) is a selective orexin 2 receptor agonist. It is a small-molecule compound and is administered intravenously. The compound was found to dose-dependently produce wakefulness to a similar degree as mo ...

and TAK-994) *

CE-123 CE-123 is an analog of modafinil, the most researched of a series of structurally related heterocyclic derivatives. In animal studies, CE-123 was found to improve performance on tests of learning and memory in a manner consistent with a nootropic ...

is under patent by

Red Bull Red Bull is a brand of energy drinks of Austrian company Red Bull GmbH. With 38% market share, it is the most popular energy drink brand as of 2019. Since its launch in 1987, more than 100 billion cans of Red Bull have been sold worldwide, inc ...

References

{{Stimulants Drug classes defined by psychological effects Nootropics