List of investigational insomnia drugs
Investigational insomnia drugs
From Wikipedia, the free encyclopedia
This is a list of investigational insomnia drugs, or drugs that are currently under development for clinical use for the treatment of insomnia but are not yet approved. They may also be referred to as investigational hypnotics.
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 [Reference]".
This list was last comprehensively updated in September 2025. It is likely to become outdated with time.
Under development
Preregistration
- Tasimelteon (Hetlioz; BMS-214778; VEC-162) – melatonin MT1 and MT2 receptor agonist[1]
Phase 3
- Brexpiprazole (Rexulti; Lu-AF41156; OPC-34712; OPDC-34712) – atypical antipsychotic (non-selective monoamine receptor modulator)[2]
- Diphenhydramine/lorazepam/zolpidem (SM-1; SM1) – combination of diphenhydramine (antihistamine and anticholinergic), lorazepam (benzodiazepine and GABAA receptor positive allosteric modulator), and zolpidem (nonbenzodiazepine/Z-drug and GABAA receptor positive allosteric modulator)[3]
- Fazamorexant (YZJ-1139) – orexin OX1 and OX2 receptor antagonist[4]
- Vornorexant (ORN-0829; TS-142) – orexin OX1 and OX2 receptor antagonist[5]
- Zuranolone (BIIB-125; S-812217; SAGE-217; SGE-797; Zurzuvae) – GABAA receptor positive allosteric modulator and neurosteroid[6]
Phase 2
- Lumateperone (Caplyta; ITI-007; ITI-722) – atypical antipsychotic (non-selective monoamine receptor modulator)[7]
- Pimavanserin (Nuplazid; ACP-103; BVF-048) – serotonin 5-HT2A receptor antagonist[8]
- Piromelatine (Neu-P11) – melatonin MT1 and MT2 receptor agonist, serotonin 5-HT1A and 5-HT1D receptor agonist, and serotonin 5-HT2B receptor antagonist[9]
- Seltorexant (JNJ-42847922; JNJ-7922; MIN-202) – orexin OX2 receptor antagonist[10]
- Sunobinop (IMB-115; IT-1315; RSC117957; S-117957; V-117957) – nociceptin receptor agonist[11]
- Tasipimidine (ODM-105) – α2A-adrenergic receptor agonist[12]
- Trazodone extended-release (AF-1161; DDS-04A; Oleptro; Triticum AC; Trittico) – serotonin 5-HT1A receptor partial agonist, serotonin 5-HT2A and 5-HT2C receptor antagonist, α1- and α2-adrenergic receptor antagonist, weak serotonin reuptake inhibitor, and other actions[13]
Phase 1/2
- SVT-4A1011 – microbiome modulator and live microbial therapeutic[14]
Preclinical
Not under development
No development reported
- Filorexant (MK-6096) – orexin OX1 and OX2 receptor antagonist[19]
- HEC-83518 – orexin receptor antagonist[20][21]
- IN-AQUL-001 – undefined mechanism of action[22][23]
- JNJ-48816274 – orexin OX2 receptor antagonist[24]
- Lirequinil (RO-413696) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/benzoquinolizinone [25]
- Lorediplon (GF-015535-00) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine[26]
- MK-1064 – orexin OX2 receptor antagonist[27]
- Research programme: psychophysiological insomnia therapeutics - Neurim Pharmaceuticals – melatonin and serotonin receptor agonists[28]
- Zolpidem topical gel (TR-396) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[29]
Discontinued
- ACT-462206 – orexin OX1 and OX2 receptor antagonist[30]
- Adipiplon (NG-273) – GABAA receptor positive allosteric modulator[31]
- ADX-10061 (NNC 01-0687; CEE-03-310; NNC-687) – dopamine D1 receptor antagonist[32][33][34]
- Almorexant (ACT-078573) – orexin OX1 and OX2 receptor antagonist[35]
- ANPH-101 – undefined mechanism of action[36]
- Atagabalin (PD-0200390) – gabapentinoid (α2δ voltage-gated calcium channel ligand)[37]
- Eplivanserin (Ciltyri; Sliwens; SR–46349; SR–46349B; SR–46615A) – serotonin 5-HT2A receptor antagonist[38]
- Esmirtazapine (ORG-50081; SCH-900265; (S)-mirtazapine) – histamine H1 receptor antagonist, serotonin 5-HT2 receptor antagonist, and α2-adrenergic receptor antagonist[39]
- Gaboxadol (LU-02030; LU-2-030; MK-0928; OV-101; THIP) – GABAA receptor agonist[40]
- GT-2203 – histamine H3 receptor agonist[41]
- Indiplon (NBI-34060) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine[42][43][44]
- LY-2624803 (HY-10275) – histamine H1 receptor inverse agonist and serotonin 5-HT2A receptor antagonist[45]
- Nabilone (Cesamet) – cannabinoid CB1 and CB2 receptor agonist[46]
- NBI-75043 – antihistamine (histamine H1 receptor antagonist)[47]
- Nelotanserin (APD-125; RVT-102) – serotonin 5-HT2A receptor antagonist[48]
- NGD-962 (NGD 96-2) – GABAA receptor modulator[49]
- Paliperidone (Invega; JNS-007ER; RO-76477; 9-hydroxyrisperidone) – atypical antipsychotic (non-selective monoamine receptor modulator)[50]
- PD-0299685 (PF-299685) – gabapentinoid (α2δ voltage-gated calcium channel ligand)[51]
- Pruvanserin (EMD-281014; LY-2422347; LSN-2411347) – serotonin 5-HT2A receptor antagonist[52]
- Remimazolam (HR-7056; Byfavo) – GABAA receptor positive allosteric modulator and benzodiazepine[53]
- Seganserin (R-56413) – serotonin 5-HT2A and 5-HT2C receptor antagonist[54]
- Suvecaltamide (CX-8998; JZP-385; MK-8998) – T-type calcium channel inhibitor[55]
- Tesamorelin (Egrifta; MDVTM; TH-9507; ThGRF 1-44) – growth hormone-releasing hormone (GHRH) receptor agonist[56]
- Tiagabine (A-70569; CEP-6671; Gabitril; NO-050328; NO-328) – GABA transporter 1 (GAT-1) blocker and GABA reuptake inhibitor[57]
- Triazolam intranasal (Hypnostat; TGAR01H) – GABAA receptor positive allosteric modulator and benzodiazepine[58]
- Volinanserin (M-100907; MDL-100907) – serotonin 5-HT2A receptor antagonist[59]
Clinically used drugs
Approved drugs
GABAA receptor positive allosteric modulators
Benzodiazepines
- Dimdazenil (Junoenil; EVT-201) – GABAA receptor partial positive allosteric modulator and benzodiazepine[60][61][62]
- Quazepam (Doral; SCH-16134) – GABAA receptor positive allosteric modulator and benzodiazepine[63][64]
- Other benzodiazepines (GABAA receptor positive allosteric modulators) (e.g., estazolam, flurazepam, temazepam, triazolam, others)[65][64]
Nonbenzodiazepines/Z-drugs
- Eszopiclone (Esopiclone; Estorra; Lunesta; Lunivia; S-Zopiclone; SEP-0227018; SEP-190; SEP-225441) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[66]
- Zaleplon (Sonata; Zerene; CL–284846; L–846; LJC–10846) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[67]
- Zolpidem extended-release (Ambien CR; FK-199B; Stilnox; Zolpidem XR) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[68]
- Zolpidem oral spray (Zolpimist) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[69]
Orexin receptor antagonists
- Daridorexant (Quviviq; ACT-541468; nemorexant) – orexin OX1 and OX2 receptor antagonist[70]
- Lemborexant (Dayvigo; E-2006) – orexin OX1 and OX2 receptor antagonist[71]
- Suvorexant (Belsomra; MK-4305) – orexin OX1 and OX2 receptor antagonist[72]
Melatonin receptor agonists
Other drugs
- Doxepin low dose (Silenor; SO-101) – antihistamine (histamine H1 receptor antagonist)[75]
- Niaprazine (Nopron) – serotonin 5-HT2A receptor antagonist and α1-adrenergic receptor antagonist
- Phenibut (Anvifen) – GABAB receptor agonist and gabapentinoid (α2δ voltage-gated calcium channel ligand)
- Tetrahydrocannabinol/cannabinol/cannabidiol (THC/CBN/CBD; Zenivol; ZTL-101) – combination of tetrahydrocannabinol (THC) (cannabinoid), cannabinol (CBN) (cannabinoid), and cannabidiol (CBD) (cannabinoid)[76][77]
Discontinued drugs
GABAA receptor positive allosteric modulators
- Barbiturates (e.g., amobarbital, pentobarbital, phenobarbital, secobarbital) – GABAA receptor positive allosteric modulators
- Piperidinediones (e.g., glutethimide) – GABAA receptor positive allosteric modulators
- Quinazolinones (e.g., methaqualone) – GABAA receptor positive allosteric modulators
Other drugs
- Fenadiazole (phénadiazole; Hypnazol, Eudormil, Viodor) – unknown mechanism of action
Off-label drugs
- α1-Adrenergic receptor antagonists (e.g., prazosin)[78][79]
- α2-Adrenergic receptor agonists (e.g., clonidine, tizanidine)[80][81][82][83][84][85][86]
- Agomelatine (Valdoxan, Thymanax) – melatonin MT1 and MT2 receptor agonist and weak serotonin 5-HT2C receptor antagonist[79]
- Amanita muscaria or muscimol – GABAA receptor agonist[87][88]
- Antihistamines (histamine H1 receptor antagonists) (e.g., diphenhydramine, doxylamine, hydroxyzine, cyproheptadine, promethazine)[65][89]
- Atypical antipsychotics (e.g., quetiapine, olanzapine, risperidone)[79]
- Cannabinoids (cannabinoid receptor modulators) (e.g., cannabis, dronabinol/tetrahydrocannabinol (THC), cannabidiol (CBD))[90]
- Gabapentinoids (α2δ voltage-gated calcium channel ligands) (e.g., gabapentin, pregabalin, gabapentin enacarbil)[79]
- Herbal supplements (e.g., chamomile, kava, lavender, passion flower, theanine, valerian)
- Melatonin (over-the-counter) – melatonin MT1 and MT2 receptor agonist
- Neurosteroids (GABAA receptor positive allosteric modulators) (e.g., oral progesterone)[91]
- Serotonin precursors (indirect serotonin receptor agonists) (e.g., tryptophan, 5-HTP)[92][93]
- Tetracyclic antidepressants (TeCAs) (e.g., mirtazapine)[79]
- Trazodone (Desyrel) – serotonin 5-HT1A receptor partial agonist, serotonin 5-HT2A and 5-HT2C receptor antagonist, α1- and α2-adrenergic receptor antagonist, weak serotonin reuptake inhibitor, and other actions[79]
- Tricyclic antidepressants (TCAs) (e.g., amitriptyline, high-dose doxepin, trimipramine)[79]