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 It is likely to become outdated with time.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 Reboxetine (AXS-12) – norepinephrine reuptake inhibitor (NRI) – narcolepsy Sodium oxybate (Xyrem) controlled release (TRN-257) – GABAB receptor agonist and GHB receptor agonist – narcolepsy, idiopathic hypersomnia
Phase 3 Alixorexton (ALKS-2680) – orexin OX2 receptor agonist – narcolepsy Pitolisant (BF-2.649; BF-2649; HBS-201; Ozawade; tiprolisant; Wakix) – histamine H3 receptor antagonist – idiopathic hypersomnia Sodium oxybate micropump (FT-218; Lumryz; ON-SXB) – GABAB receptor agonist and GHB receptor agonist – idiopathic hypersomnia
Phase 2/3 Balumorexton (TAK-360) – orexin OX2 receptor agonist – narcolepsy, idiopathic hypersomnia
Phase 2 Alixorexton (ALKS-2680) – orexin OX2 receptor agonist – idiopathic hypersomnia Cleminorexton (ORX750; ORX-750) – orexin OX2 receptor agonist – narcolepsy, idiopathic hypersomnia Firazorexton (TAK-994) – orexin OX2 receptor agonist – narcolepsy Flecainide/modafinil (THN-102) – combination of flecainide (sodium channel blocker) and modafinil (atypical dopamine reuptake inhibitor) – narcolepsy Ledasorexton (E-2086) – orexin OX2 receptor agonist – narcolepsy Mazindol controlled release (NLS-0; NLS-1; NLS-10; NLS-13; NLS-2; Nolazol; Quilience) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) – narcolepsy, idiopathic hypersomnia Pentylenetetrazole (BTD-001; pentetrazol; PTZ) – GABAA receptor antagonist – narcolepsy, idiopathic hypersomnia Samelisant (SUVN-G3031) – histamine H3 receptor antagonist – narcolepsy Serdexmethylphenidate (KP-484; KP-1077; KP-879) – norepinephrine–dopamine reuptake inhibitor (NDRI) – idiopathic hypersomnia
Phase 1/2 Serdexmethylphenidate (KP-484; KP-1077; KP-879) – norepinephrine–dopamine reuptake inhibitor (NDRI) – narcolepsy
Phase 1 Lu-AH69593 – undefined mechanism of action – narcolepsy MK-6552 – undefined mechanism of action – narcolepsy ORX-142 – orexin OX2 receptor agonist Sodium oxybate once-nightly – GABAB receptor agonist and GHB receptor agonist – narcolepsy Valiloxybate (XW-10172) – GABAB receptor agonist and GHB receptor agonist – narcolepsy
Preclinical AEX-2 – orexin OX1 and OX2 receptor agonist – narcolepsy HBS-102 (CSTI-100) – melanin-concentrating hormone receptor 1 (MCHR1) antagonist – narcolepsy Methylphenidate transdermal (Defent) – norepinephrine–dopamine reuptake inhibitor (NDRI) – narcolepsy NLS-11 – undefined mechanism of action – Kleine–Levin syndrome
Research AEX-19 – orexin OX1 and OX2 receptor agonist – narcolepsy, idiopathic hypersomnia SPN-446 – undefined mechanism of action – narcolepsy
Not under development No development reported Armesocarb (MLR-1019; (R)-mesocarb) – atypical dopamine reuptake inhibitor (DRI) – sleep disorders Danavorexton (TAK-925) – orexin OX2 receptor agonist – idiopathic hypersomnia Flecainide/modafinil (THN-102) – combination of flecainide (sodium channel blocker) and modafinil (atypical dopamine reuptake inhibitor (DRI)) – hypersomnia Flmodafinil (CRL-40,940; NLS-14; NLS-4; JBG01-41; bisfluoromodafinil; lauflumide) – atypical dopamine reuptake inhibitor (DRI) – idiopathic hypersomnia Golexanolone (GR-3027) – GABAA receptor negative allosteric modulator and neurosteroid – idiopathic hypersomnia GSK-189254 (GSK-189254A) – histamine H3 receptor antagonist – narcolepsy JZP-386 (C-10323; deuterated sodium oxybate; deuterated GHB) – GABAB receptor agonist and GHB receptor agonist – narcolepsy Research programme: neurological diseases therapies - Inexia/Nxera Pharma – orexin OX1 and OX2 receptor agonists – narcolepsy Research programme: small molecule therapeutics - Orexia/X-Chem – orexin OX2 receptor agonists SLS-010 – histamine H3 receptor antagonist – narcolepsy Sodium oxybate controlled release (GHB) – GABAB receptor agonist and GHB receptor agonist – narcolepsy Solriamfetol (YKP-10A; YKP10A; R–228060) – undefined mechanism of action – narcolepsy Valiloxibic acid (XWL-008) – undefined mechanism of action – narcolepsy
Discontinued ABT-652 – histamine H3 receptor modulator – sleep disorders Bavisant (BEN-2001; JNJ-1074; JNJ-31001074) – histamine H3 receptor antagonist – narcolepsy Cipralisant (GT-2331; Perceptin) – histamine H3 receptor antagonist – sleep disorders Danavorexton (TAK-925) – orexin OX2 receptor agonist – narcolepsy Enerisant (TS-091; TS-0911; TS091) – histamine H3 receptor antagonist – narcolepsy and hypersomnia Flmodafinil (CRL-40,940; NLS-14; NLS-4; JBG01-41; bisfluoromodafinil; lauflumide) – atypical dopamine reuptake inhibitor (DRI) – narcolepsy JNJ-17216498 – histamine H3 receptor antagonist – narcolepsy Lisdexamfetamine (LDX; Elvanse; NRP-104; S-877489; SHP-489; SPD-489; Tyvense; Venvanse; Vyvanse) – norepinephrine–dopamine releasing agent (NDRA) – sleep disorders LML-134 (LML134) – histamine H3 receptor antagonist – sleep disorders Oveporexton (TAK-861) – orexin OX2 receptor agonist – idiopathic hypersomnia Phacetoperane (NLS-3) – norepinephrine–dopamine reuptake inhibitor (NDRI) – narcolepsy Research programme: sleep disorder therapeutics - Servier (S-41150) – histamine H3 receptor antagonist – sleep disorders SAR-152954 (SAR152954) – histamine H3 receptor antagonist – sleep disorders Ulotaront (SEP-363856; SEP-856) – trace amine-associated receptor 1 (TAAR1) agonist and serotonin 5-HT1A and 5-HT1D receptor partial agonist – narcolepsy
Formal development never or not yet started Mevidalen (LY-3154207; D1 PAM) – dopamine D1 receptor positive allosteric modulator
Clinically used drugs Approved drugs Catecholaminergic agents Armodafinil (CEP-10953; Nuvigil; (R)-modafinil) – atypical dopamine reuptake inhibitor (DRI) – hypersomnia Modafinil (AFT-801; Alertec; Attenace; CN-801; CRL-40476; Modasamil; Modasonil; Modavigil; Modiodal; Provigil; Sparlon; Vigil) – atypical dopamine reuptake inhibitor (DRI) – narcolepsy, hypersomnia 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
Oxybate/GHB drugs Calcium/magnesium/potassium/sodium oxybates (GHB; JZP-258; Xywav; oxybate mixed salt solution; lower-sodium oxybate) – GABAB receptor agonist and GHB receptor agonist – narcolepsy and idiopathic hypersomnia Sodium oxybate (GHB; JZP-6; KEY-10; Xyrem) – GABAB receptor agonist and GHB receptor agonist – narcolepsy Sodium oxybate (GHB; FT-218; Lumryz; ON-SXB) – GABAB receptor agonist and GHB receptor agonist – narcolepsy
Histamine H3 receptor antagonists Pitolisant (BF-2.649; BF-2649; HBS-201; Ozawade; tiprolisant; Wakix) – histamine H3 receptor antagonist – narcolepsy, hypersomnia
Orexin receptor agonists Oveporexton (Orzeyful; TAK-861) – orexin OX2 receptor agonist – narcolepsy
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