Eugeroic

Last updated
Eugeroic
Drug class
Modafinil.svg
The chemical structure of modafinil, the prototypical drug of this class
Class identifiers
Synonyms Eugrégorique; Eugregorique; Eugregoric; Vigilance-promoting agent
UseTo increase wakefulness and arousal, to reduce sleepiness and sedation
ATC code N06B
Legal status
In Wikidata

A eugeroic, or eugregoric, also known as a vigilance-promoting agent, is a type of drug that increases vigilance (that is, alertness and/or wakefulness). [1] [2] [3] [4] The term has been used inconsistently and in multiple ways in the scientific literature, either to refer specifically to modafinil-type wakefulness-promoting agents or to refer to wakefulness-promoting agents generally. [1] [5] [6] [7] It was first introduced in the French literature in 1987 as a descriptor for modafinil-like wakefulness-promoting drugs and for purposes of distinguishing such drugs from psychostimulants. [1] However, the term "eugeroic" has not been widely adopted in the literature, and instead the term "wakefulness-promoting agent" (and variations thereof) has been more widely used, both for modafinil-type drugs and other agents. [1] [8] [9] [10]

Contents

Eugeroics, in the sense of modafinil-type wakefulness promoting agents, include modafinil itself, armodafinil, and adrafinil, among others. [9] They are medically indicated for the treatment of certain sleep disorders, including excessive daytime sleepiness (EDS) in narcolepsy or obstructive sleep apnea (OSA). [3] [4] Eugeroics are also often prescribed off-label for the treatment of EDS in idiopathic hypersomnia. [11] In contrast to classical psychostimulants, such as amphetamine and methylphenidate, which are also used in the treatment of these disorders, eugeroics typically do not produce euphoria, and, consequently, have lower misuse potential. [3] [4] [12]

Modafinil and armodafinil are thought to act as selective, weak, atypical dopamine reuptake inhibitors (DRIs). [13] [3] [4] However, additional actions are also possible and have not been ruled out. [13] Adrafinil acts as a prodrug of modafinil and hence shares its mechanism of action. [13] Certain other drugs acting as atypical DRIs with known or potential wakefulness-promoting effects include solriamfetol (also a norepinephrine reuptake inhibitor), [14] [15] vanoxerine, [16] phenylpiracetam, [17] [18] [19] and mesocarb. [20] [21] [22] [23] Other wakefulness-promoting agents act in a variety of other ways. [16] [1] [10] [24]

List of eugeroics

Marketed

Discontinued

Never marketed

Novel eugeroics

The pharmaceutical company Cephalon, the original United States market rights holder of modafinil, has demonstrated initiative in the development of a successor to the prototypical eugeroic. [25] Of the more than twenty compounds preclinically tested in Cephalon's three-part drug discovery series, the compound fluorenol was selected as a lead. [26] Fluorenol was found to induce wakefulness to a greater degree than modafinil, despite possessing a lower affinity for the dopamine transporter (DAT). [26] Many other modafinil analogues have also subsequently been developed, not specifically as wakefulness-promoting agents but for treatment of conditions like psychostimulant use disorder and motivational disorders. [27] [28] [29] [17]

Related Research Articles

<span class="mw-page-title-main">Modafinil</span> Eugeroic medication

Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant and eugeroic medication used primarily to treat narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and sudden sleep attacks. Modafinil is also approved for stimulating wakefulness in people with sleep apnea and shift work sleep disorder. It is taken by mouth. Modafinil is not approved by the US Food and Drug Administration (FDA) for use in people under 17 years old.

A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.

<span class="mw-page-title-main">Adrafinil</span> Wakefulness-promoting drug

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 who wished to avoid fatigue, such as night workers or others who needed to stay awake and alert for long periods of time. Additionally, the medication has been used non-medically as a novel vigilance-promoting agent.

<span class="mw-page-title-main">Dopamine transporter</span> Mammalian protein found in Homo sapiens

The dopamine transporter is a membrane-spanning protein coded for in humans by the SLC6A3 gene, that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopamine into vesicles for storage and later release. Dopamine reuptake via DAT provides the primary mechanism through which dopamine is cleared from synapses, although there may be an exception in the prefrontal cortex, where evidence points to a possibly larger role of the norepinephrine transporter.

Racetams, also sometimes known simply as pyrrolidones, are a class of drugs that share a pyrrolidone nucleus. Many, but not all, specifically have a 2-oxo-1-pyrrolidine acetamide (piracetam) nucleus. Some racetams, such as piracetam, aniracetam, oxiracetam, pramiracetam, and phenylpiracetam, are considered nootropics. Phenylpiracetam is also a stimulant. Others, such as levetiracetam, brivaracetam, and seletracetam, are anticonvulsants.

<span class="mw-page-title-main">Phenylpiracetam</span> Chemical compound

Phenylpiracetam, also known as fonturacetam and sold under the brand names Phenotropil, Actitropil, and Carphedon among others, is a stimulant and nootropic medication used in Russia and certain other Eastern European countries in the treatment of cerebrovascular deficiency, depression, apathy, and attention, and memory problems, among other indications. It is also used in Russian cosmonauts to improve physical, mental, and cognitive abilities. The drug is taken by mouth.

<span class="mw-page-title-main">Armodafinil</span> Eugeroic medication

Armodafinil, sold under the brand name Nuvigil, is a wakefulness-promoting medication which is used to treat excessive daytime sleepiness associated with obstructive sleep apnea, narcolepsy, and shift work disorder. It is also used off-label for certain other indications. The drug is taken by mouth.

<span class="mw-page-title-main">Fluorenol</span> Chemical compound

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 converted to fluorenone by oxidation. It is a white-cream colored solid at room temperature.

A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain.

<span class="mw-page-title-main">Wakefulness-promoting agent</span> Drug that increases wakefulness

A wakefulness-promoting agent (WPA), or wake-promoting agent, is a drug that increases wakefulness and arousal. They are similar to but distinct from psychostimulants, which not only promote wakefulness but also produce other more overt central nervous system effects, such as improved mood, energy, and motivation. Wakefulness-promoting agents are used to treat narcolepsy and hypersomnia as well as to promote wakefulness and increase performance in healthy people.

<span class="mw-page-title-main">Fladrafinil</span> Wakefulness-promoting drug

Fladrafinil, also known as fluorafinil or as bisfluoroadrafinil, is a wakefulness-promoting agent related to modafinil that was never marketed. It is sold online and used non-medically as a nootropic.

<span class="mw-page-title-main">Flmodafinil</span> Wakefulness-promoting drug/Dopamine reuptake inhibitor

Flmodafinil, also known as bisfluoromodafinil and lauflumide, is a wakefulness-promoting agent related to modafinil which has been developed for treatment of a variety of different medical conditions. These include chronic fatigue syndrome, idiopathic hypersomnia, narcolepsy, attention deficit hyperactivity disorder (ADHD), and Alzheimer's disease. Aside its development as a potential pharmaceutical drug, flmodafinil is sold online and used non-medically as a nootropic.

<span class="mw-page-title-main">Solriamfetol</span> Medication used for the treatment of excessive sleepiness

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.

<span class="mw-page-title-main">Esmodafinil</span> Unmarketed enantiomer of modafinil

Esmodafinil (also known as (S)-modafinil or (+)-modafinil; developmental code name CRL-40983) is the enantiopure (S)-(+)-enantiomer of modafinil. Unlike armodafinil ((R)-(–)-modafinil), esmodafinil has never been marketed on its own.

<span class="mw-page-title-main">MRZ-9547</span> Dopamine reuptake inhibitor that was under development for fatigue in Parkinsons disease

MRZ-9547, also known as (R)-phenylpiracetam, (R)-phenotropil, or (R)-fonturacetam, is a selective dopamine reuptake inhibitor (IC50Tooltip half-maximal inhibitory concentration = 14.5 μM) that was developed by Merz Pharma. It is the (R)-enantiomer of the racetam and nootropic phenylpiracetam (phenotropil; fonturacetam).

<span class="mw-page-title-main">Modafiendz</span> Wakefulness-promoting drug related to modafinil

Modafiendz, also known as N-methyl-4,4-difluoromodafinil or as N-methylbisfluoromodafinil, is a wakefulness-promoting agent related to modafinil that was never marketed. It is sold online and used non-medically as a nootropic.

<span class="mw-page-title-main">JJC8-088</span> Cocaine-like dopamine reuptake inhibitor derived from modafinil

JJC8-088 is a dopamine reuptake inhibitor (DRI) that was derived from the wakefulness-promoting agent modafinil.

(<i>S</i>)-MK-26 An atypical dopamine reuptake inhibitor with pro-motivational effects related to modafinil

(S)-MK-26 is an atypical dopamine reuptake inhibitor (DRI) that was derived from modafinil. It is closely related to two other modafinil analogues, (S,S)-CE-158 and (S)-CE-123.

Armesocarb (developmental code name MLR-1019), also known as (R)-mesocarb or L-mesocarb, is a selective atypical dopamine reuptake inhibitor (DRI). It is currently under development for the treatment of Parkinson's disease and sleep disorders.

References

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