From Wikipedia, the free encyclopedia
Drug for wakefulness and alertness
Eugeroics (originally "eugrégorique" or "eugregoric"),
[1] also known as wakefulness-promoting agents and wakefulness-promoting drugs , are a class of
drugs that promote
wakefulness and
alertness .
[2]
[3] They are medically indicated for the
treatment of certain
sleep disorders including
excessive daytime sleepiness (EDS) in
narcolepsy or
obstructive sleep apnea (OSA) .
[2]
[3] Eugeroics are also often prescribed
off-label for the treatment of EDS in
idiopathic hypersomnia .
[4] In contrast to classical
psychostimulants , such as
methylphenidate and
amphetamine , which are also used in the treatment of these disorders, eugeroics typically do not produce marked
euphoria , and, consequently, have a lower
addictive potential .
[2]
[3]
[5]
Modafinil and
armodafinil are each thought to act as selective, weak, atypical
dopamine reuptake inhibitors (DRI) ,
[2]
[3] whereas
adrafinil acts as a
prodrug for modafinil. Other eugeroics include
solriamfetol , which acts as a
norepinephrine–dopamine reuptake inhibitor (NDRI) ,
[6]
[7] and
pitolisant , which acts as a
histamine 3 (H3 ) receptor antagonist /
inverse agonist .
[8]
[9]
[10]
Recent research
Cephalon, the original U.S. market rights holder of modafinil, has demonstrated initiative in the development of a successor to the prototypical eugeroic.
[11] Of the more than twenty compounds preclinically tested in Cephalon's three-part drug discovery series, the compound
fluorenol was selected as a lead. Fluorenol was found to induce wakefulness to a greater degree than modafinil, despite possessing a lower affinity for the
dopamine transporter .
[12]
All currently marketed eugeroics are classified as
central nervous system stimulants and possess some (attenuated)
stimulant -like properties.
[13]
[14] It is expected that future developments will further distinguish eugeroics from classical CNS stimulants.
[15]
[11]
Examples
Marketed
Discontinued
Never marketed
In development
References
^ Milgram, Norton W.; Callahan, Heather; Siwak, Christina (2006).
"Adrafinil: A Novel Vigilance Promoting Agent" . CNS Drug Reviews . 5 (3): 193–212.
doi :
10.1111/j.1527-3458.1999.tb00100.x .
ISSN
1080-563X .
^
a
b
c
d
"Provigil: Prescribing information" (PDF) . United States Food and Drug Administration . Cephalon, Inc. January 2015. Retrieved 16 August 2015 .
^
a
b
c
d
"Nuvigil: Prescribing information" (PDF) . United States Food and Drug Administration . Cephalon, Inc. April 2015. Retrieved 16 August 2015 .
^
"Practice Parameters for the Treatment of Narcolepsy and other Hypersomnias of Central Origin" (PDF) . American Academy of Sleep Medicine (AASM) . September 2007.
^ Taneja, Indu; Haman, Kirsten; Shelton, Richard C.; Robertson, David (February 2007).
"A randomized, double-blind, crossover trial of modafinil on mood" . Journal of Clinical Psychopharmacology . 27 (1): 76–79.
doi :
10.1097/jcp.0b013e31802eb7ea .
ISSN
0271-0749 .
PMID
17224718 .
S2CID
40801601 .
^ Stahl, Stephen M.; Pradko, James F.; Haight, Barbara R.; Modell, Jack G.; Rockett, Carol B.; Learned-Coughlin, Susan (2004-08-13).
"A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor" . The Primary Care Companion to the Journal of Clinical Psychiatry . 06 (4): 159–166.
doi :
10.4088/PCC.v06n0403 .
ISSN
1523-5998 .
PMC
514842 .
PMID
15361919 .
^ Stahl, Stephen M. (2009-03-02).
Stahl's Illustrated Antidepressants . Cambridge University Press.
ISBN
978-0-521-75852-9 .
^ Schwartz, Jean-Charles (2011).
"The histamine H3 receptor: from discovery to clinical trials with pitolisant: H3 Receptor: from discovery to clinical trials" . British Journal of Pharmacology . 163 (4): 713–721.
doi :
10.1111/j.1476-5381.2011.01286.x .
PMC
3111674 .
PMID
21615387 .
^ Kollb-Sielecka, Marta; Demolis, Pierre; Emmerich, Joseph; Markey, Greg; Salmonson, Tomas; Haas, Manuel (2017).
"The European Medicines Agency review of pitolisant for treatment of narcolepsy: summary of the scientific assessment by the Committee for Medicinal Products for Human Use" . Sleep Medicine . 33 : 125–129.
doi :
10.1016/j.sleep.2017.01.002 .
PMID
28449891 .
^ Inocente, Clara; Arnulf, Isabelle; Bastuji, Hélène; Thibault-Stoll, Anne; Raoux, Aude; Reimão, Rubens; Lin, Jian-Sheng; Franco, Patricia (2012).
"Pitolisant, an Inverse Agonist of the Histamine H3 Receptor: An Alternative Stimulant for Narcolepsy-Cataplexy in Teenagers With Refractory Sleepiness" . Clinical Neuropharmacology . 35 (2): 55–60.
doi :
10.1097/WNF.0b013e318246879d .
ISSN
0362-5664 .
PMID
22356925 .
S2CID
36336966 .
^
a
b Dunn, Derek; Hostetler, Greg; Iqbal, Mohamed; Messina-McLaughlin, Patricia; Reiboldt, Alyssa; Lin, Yin Guo; Gruner, John; Bacon, Edward R.; Ator, Mark A.; Chatterjee, Sankar (2012-03-15).
"Wake-promoting agents: search for next generation modafinil: part I" . Bioorganic & Medicinal Chemistry Letters . 22 (6): 2312–2314.
doi :
10.1016/j.bmcl.2011.12.099 .
ISSN
1464-3405 .
PMID
22264475 .
^ Dunn, Derek; Hostetler, Greg; Iqbal, Mohamed; Marcy, Val R.; Lin, Yin Guo; Jones, Bruce; Aimone, Lisa D.; Gruner, John; Ator, Mark A.; Bacon, Edward R.; Chatterjee, Sankar (2012-06-01).
"Wake promoting agents: Search for next generation modafinil, lessons learned: Part III" . Bioorganic & Medicinal Chemistry Letters . 22 (11): 3751–3753.
doi :
10.1016/j.bmcl.2012.04.031 .
ISSN
0960-894X .
PMID
22546675 .
^ Inocente, Clara; Arnulf, Isabelle; Bastuji, Hélène; Thibault-Stoll, Anne; Raoux, Aude; Reimão, Rubens; Lin, Jian-Sheng; Franco, Patricia (2012).
"Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness" . Clinical Neuropharmacology . 35 (2): 55–60.
doi :
10.1097/WNF.0b013e318246879d .
ISSN
1537-162X .
PMID
22356925 .
S2CID
36336966 .
^
a
b
"What is SUNOSI® (solriamfetol) Treatment ? | SUNOSI® for Patients" . www.sunosi.com . Retrieved 2020-01-03 .
^ Kim, Dongsoo (2012-02-22).
"Practical Use and Risk of Modafinil, a Novel Waking Drug" . Environmental Health and Toxicology . 27 : e2012007.
doi :
10.5620/eht.2012.27.e2012007 .
ISSN
2233-6567 .
PMC
3286657 .
PMID
22375280 .
^
"How WAKIX Works | WAKIX® (pitolisant) tablets" . wakix.com . Retrieved 2020-01-03 .
^
"New Data Presented at World Sleep Congress Demonstrate Early Signs of Efficacy for TAK-925, a Selective Orexin Type-2 Receptor (OX2R) Agonist, in Patients with Narcolepsy Type 1" . www.takeda.com . Retrieved 2019-12-06 .
^
"Thiazole and diphenyl substituted sulfoxides for use in improving cognition functions and against addictions to substances. - Patent EP-3792252-A1 - PubChem" . pubchem.ncbi.nlm.nih.gov . Retrieved 2022-09-26 .