Eugeroics (originally "eugrégorique" or "eugregoric"),
also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of
drugs 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 ...
.
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 tests ...
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 affect ...
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 ...
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). 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 exten ...
and
amphetamine, which are also used in the treatment of these disorders, eugeroics typically do not produce
euphoria, and, consequently, have a lower
addictive potential.
Modafinil 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 In ...
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 heada ...
, 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 commerc ...
, which acts as a
histamine 3 (H3) receptor antagonist/
inverse agonist.
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 In ...
(Nuvigil)
*
Modafinil (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 commerc ...
(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 heada ...
(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 (also known as flmodafinil, bisfluoromodafinil and lauflumide) is the bisfluoro analog of modafinil. It is a eugeroic as well as a weak dopamine reuptake inhibitor. Its inventors claim that it is more effective than modafinil and adra ...
(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 be ...
* Methylbisfluoromodafinil
*
2-Phenyl-3-aminobutane
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 ...
agonists (two are currently under development by
,
danavorexton and
TAK-994
TAK-994 is an orexin receptor agonist which is under development by Takeda for the treatment of narcolepsy. It is a small-molecule and orally active compound and acts as a highly selective agonist of the orexin receptor 2 (OX2) (>700-fold select ...
)
*
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.
References
{{Stimulants
Drug classes defined by psychological effects
Nootropics