List of investigational narcolepsy and hypersomnia drugs

This is a list of investigational narcolepsy and hypersomnia drugs, or drugs that are currently under development for clinical use for the treatment of narcolepsy and/or hypersomnia (e.g., excessive daytime sleepiness, idiopathic hypersomnia) but are not yet approved. Many of them may also be referred to as investigational wakefulness-promoting agents (WPAs).

Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action – Indication [Reference]".

This list was last comprehensively updated in September 2025. It is likely to become outdated with time.

Under development

Preregistration

• Sodium oxybate controlled release (TRN-257) – GABA_B receptor agonist and GHB receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800071993

Phase 3

• Oveporexton (TAK-861) – orexin OX₂ receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800063888
• Reboxetine (AXS-12) – norepinephrine reuptake inhibitor (NRI) – narcolepsy https://adisinsight.springer.com/drugs/800053169
• Sodium oxybate micropump (FT-218; Lumryz; ON-SXB) – GABA_B receptor agonist and GHB receptor agonist – idiopathic hypersomnia https://adisinsight.springer.com/drugs/800041142

Phase 2

• Alixorexton (ALKS-2680) – orexin OX₂ receptor agonist – narcolepsy, idiopathic hypersomnia https://adisinsight.springer.com/drugs/800066491
• Firazorexton (TAK-994) – orexin OX₂ receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800054722
• Flecainide/modafinil (THN-102) – combination of flecainide (sodium channel blocker) and modafinil (atypical dopamine reuptake inhibitor) – narcolepsy https://adisinsight.springer.com/drugs/800045045
• Mazindol controlled release (NLS-0; NLS-1; NLS-10; NLS-13; NLS-2; Nolazol; Quilience) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) – narcolepsy, idiopathic hypersomnia https://adisinsight.springer.com/drugs/800041870
• ORX-750 – orexin OX₂ receptor agonist – narcolepsy, idiopathic hypersomnia https://adisinsight.springer.com/drugs/800073116
• Pentylenetetrazole (BTD-001; pentetrazol; PTZ) – GABA_A receptor antagonist – narcolepsy, idiopathic hypersomnia https://adisinsight.springer.com/drugs/800038901
• Samelisant (SUVN-G3031) – histamine H₃ receptor antagonist – narcolepsy https://adisinsight.springer.com/drugs/800032317
• Serdexmethylphenidate (KP-484; KP-1077; KP-879) – norepinephrine–dopamine reuptake inhibitor (NDRI) – idiopathic hypersomnia https://adisinsight.springer.com/drugs/800063410
• TAK-360 – orexin OX₂ receptor agonist – narcolepsy, idiopathic hypersomnia https://adisinsight.springer.com/drugs/800078500

Phase 1/2

• Serdexmethylphenidate (KP-484; KP-1077; KP-879) – norepinephrine–dopamine reuptake inhibitor (NDRI) – narcolepsy https://adisinsight.springer.com/drugs/800063410

Phase 1

• Danavorexton (TAK-925) – orexin OX₂ receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800050631
• E-2086 – orexin OX₂ receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800072674
• Lu-AH69593 – undefined mechanism of action – narcolepsy https://adisinsight.springer.com/drugs/800084457
• MK-6552 – undefined mechanism of action – narcolepsy https://adisinsight.springer.com/drugs/800076724
• Sodium oxybate once-nightly – GABA_B receptor agonist and GHB receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800059028
• Valiloxybate (XW-10172) – GABA_B receptor agonist and GHB receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800051495

Preclinical

• AEX-2 – orexin OX₁ and OX₂ receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800077308
• HBS-102 (CSTI-100) – melanin-concentrating hormone receptor 1 (MCHR1) antagonist – narcolepsy https://adisinsight.springer.com/drugs/800051881 https://www.prnewswire.com/news-releases/harmony-biosciences-acquires-asset-with-novel-mechanism-of-action-for-the-potential-treatment-of-narcolepsy-and-other-rare-neurological-diseases-301350524.html
• Methylphenidate transdermal (Defent) – norepinephrine–dopamine reuptake inhibitor (NDRI) – narcolepsy https://adisinsight.springer.com/drugs/800077879
• NLS-11 – undefined mechanism of action – Kleine–Levin syndrome https://adisinsight.springer.com/drugs/800052178
• ORX-142 – orexin OX₂ receptor agonist https://adisinsight.springer.com/drugs/800079210

Research

• AEX-19 – orexin OX₁ and OX₂ receptor agonist – narcolepsy, idiopathic hypersomnia https://adisinsight.springer.com/drugs/800076849
• SPN-446 – undefined mechanism of action – narcolepsy https://adisinsight.springer.com/drugs/800066181

Not under development

No development reported

• Armesocarb (MLR-1019; (R)-mesocarb) – atypical dopamine reuptake inhibitor (DRI) – sleep disorders https://adisinsight.springer.com/drugs/800034792
• Danavorexton (TAK-925) – orexin OX₂ receptor agonist – idiopathic hypersomnia https://adisinsight.springer.com/drugs/800050631
• Flecainide/modafinil (THN-102) – combination of flecainide (sodium channel blocker) and modafinil (atypical dopamine reuptake inhibitor (DRI)) – hypersomnia https://adisinsight.springer.com/drugs/800045045
• Flmodafinil (CRL-40,940; NLS-14; NLS-4; JBG01-41; bisfluoromodafinil; lauflumide) – atypical dopamine reuptake inhibitor (DRI) – idiopathic hypersomnia https://adisinsight.springer.com/drugs/800043932
• Golexanolone (GR-3027) – GABA_A receptor negative allosteric modulator and neurosteroid – idiopathic hypersomnia https://adisinsight.springer.com/drugs/800049924
• GSK-189254 (GSK-189254A) – histamine H₃ receptor antagonist – narcolepsy https://adisinsight.springer.com/drugs/800021193
• JZP-386 (C-10323; deuterated sodium oxybate; deuterated GHB) – GABA_B receptor agonist and GHB receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800041079 https://synapse.patsnap.com/drug/683b6b233a4d46288319189074ef95f7
• Oveporexton (TAK-861) – orexin OX₂ receptor agonist – idiopathic hypersomnia https://adisinsight.springer.com/drugs/800063888
• Research programme: neurological diseases therapies - Inexia/Nxera Pharma – orexin OX₁ and OX₂ receptor agonists – narcolepsy https://adisinsight.springer.com/drugs/800054011
• Research programme: small molecule therapeutics - Orexia/X-Chem – orexin OX₂ receptor agonists https://adisinsight.springer.com/drugs/800050960
• SLS-010 – histamine H₃ receptor antagonist – narcolepsy https://adisinsight.springer.com/drugs/800032440
• Sodium oxybate controlled release (GHB) – GABA_B receptor agonist and GHB receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800069685
• Solriamfetol (YKP-10A; YKP10A; R–228060) – undefined mechanism of action – narcolepsy https://adisinsight.springer.com/drugs/800008327
• Valiloxibic acid (XWL-008) – undefined mechanism of action – narcolepsy https://adisinsight.springer.com/drugs/800055229

Discontinued

• ABT-652 – histamine H₃ receptor modulator – sleep disorders https://adisinsight.springer.com/drugs/800032225
• Bavisant (BEN-2001; JNJ-1074; JNJ-31001074) – histamine H₃ receptor antagonist – narcolepsy https://adisinsight.springer.com/drugs/800031762
• Cipralisant (GT-2331; Perceptin) – histamine H₃ receptor antagonist – sleep disorders https://adisinsight.springer.com/drugs/800011060
• Enerisant (TS-091; TS-0911; TS091) – histamine H₃ receptor antagonist – narcolepsy and hypersomnia https://adisinsight.springer.com/drugs/800038071
• Flmodafinil (CRL-40,940; NLS-14; NLS-4; JBG01-41; bisfluoromodafinil; lauflumide) – atypical dopamine reuptake inhibitor (DRI) – narcolepsy https://adisinsight.springer.com/drugs/800043932
• JNJ-17216498 – histamine H₃ receptor antagonist – narcolepsy https://adisinsight.springer.com/drugs/800030725
• Lisdexamfetamine (LDX; Elvanse; NRP-104; S-877489; SHP-489; SPD-489; Tyvense; Venvanse; Vyvanse) – norepinephrine–dopamine releasing agent (NDRA) – sleep disorders https://adisinsight.springer.com/drugs/800020876
• LML-134 (LML134) – histamine H₃ receptor antagonist – sleep disorders https://adisinsight.springer.com/drugs/800041905
• Phacetoperane (NLS-3) – norepinephrine–dopamine reuptake inhibitor (NDRI) – narcolepsy https://adisinsight.springer.com/drugs/800043928
• Research programme: sleep disorder therapeutics - Servier (S-41150) – histamine H₃ receptor antagonist – sleep disorders https://adisinsight.springer.com/drugs/800027486
• SAR-152954 (SAR152954) – histamine H₃ receptor antagonist – sleep disorders https://adisinsight.springer.com/drugs/800033674
• Ulotaront (SEP-363856; SEP-856) – trace amine-associated receptor 1 (TAAR1) agonist and serotonin 5-HT_1A and 5-HT_1D receptor partial agonist – narcolepsy https://adisinsight.springer.com/drugs/800036955

Formal development never or not yet started

• Mevidalen (LY-3154207; D1 PAM) – dopamine D₁ receptor positive allosteric modulator https://adisinsight.springer.com/drugs/800042093

Clinically used drugs

Approved drugs

Catecholaminergic agents

• Armodafinil (CEP-10953; Nuvigil; (R)-modafinil) – atypical dopamine reuptake inhibitor (DRI) – hypersomnia https://adisinsight.springer.com/drugs/800022302
• Modafinil (AFT-801; Alertec; Attenace; CN-801; CRL-40476; Modasamil; Modasonil; Modavigil; Modiodal; Provigil; Sparlon; Vigil) – atypical dopamine reuptake inhibitor (DRI) – narcolepsy, hypersomnia https://adisinsight.springer.com/drugs/800000667
• Solriamfetol (ADX-N05; ARL-N05; JZP-110; SKL-N05; Sunosi) – atypical norepinephrine–dopamine reuptake inhibitor (NDRI) and trace amine-associated receptor 1 (TAAR1) agonist – hypersomnia https://adisinsight.springer.com/drugs/800030225

Oxybate/GHB drugs

• Calcium/magnesium/potassium/sodium oxybates (GHB; JZP-258; Xywav; oxybate mixed salt solution; lower-sodium oxybate) – GABA_B receptor agonist and GHB receptor agonist – narcolepsy and idiopathic hypersomnia https://adisinsight.springer.com/drugs/800048256
• Sodium oxybate (GHB; JZP-6; KEY-10; Xyrem) – GABA_B receptor agonist and GHB receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800008211
• Sodium oxybate (GHB; FT-218; Lumryz; ON-SXB) – GABA_B receptor agonist and GHB receptor agonist – narcolepsy https://adisinsight.springer.com/drugs/800041142

Histamine H₃ receptor antagonists

• Pitolisant (BF-2.649; BF-2649; HBS-201; Ozawade; tiprolisant; Wakix) – histamine H₃ receptor antagonist – narcolepsy, hypersomnia https://adisinsight.springer.com/drugs/800029451

Discontinued drugs

• Adrafinil (Olmifon; CRL-40028; N-hydroxymodafinil) – atypical dopamine reuptake inhibitor (DRI) (modafinil prodrug) – hypersomnia

Off-label drugs

• Adenosine receptor antagonists (e.g., caffeine)
• Norepinephrine releasing agents (NRAs) (e.g., ephedrine, selegiline (via metabolites))
• Norepinephrine reuptake inhibitors (NRIs) (e.g., atomoxetine, reboxetine, viloxazine)
• Norepinephrine–dopamine reuptake inhibitors (NDRIs) (e.g., bupropion, nomifensine, amineptine)
• Serotonin–norepinephrine–dopamine reuptake inhibitors (SNDRIs) (e.g., mazindol)
• Stimulants (norepinephrine–dopamine releasing agents and/or reuptake inhibitors (NDRAs/NDRIs)) (e.g., amphetamine, methamphetamine, lisdexamfetamine, methylphenidate, pemoline)

See also

• List of investigational drugs
• List of investigational insomnia drugs
• List of investigational chronobiotics
• Wakefulness-promoting agent
• Stimulant

References

External links

• AdisInsight - Springer