Eugeroic
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 .