List of investigational insomnia drugs

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 It is likely to become outdated with time.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

Phase 3 Brexpiprazole (Rexulti; Lu-AF41156; OPC-34712; OPDC-34712) – atypical antipsychotic (non-selective monoamine receptor modulator) Cannabidiol soft-gel (CBD soft-gel; CBD-TPM) — cannabinoid and various actions 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) Zuranolone (BIIB-125; S-812217; SAGE-217; SGE-797; Zurzuvae) – GABAA receptor positive allosteric modulator and neurosteroid

Phase 2 Dexmedetomidine buccal (RE-03) — α2-adrenergic receptor agonist Lumateperone (Caplyta; ITI-007; ITI-722) – atypical antipsychotic (non-selective monoamine receptor modulator) Pimavanserin (Nuplazid; ACP-103; BVF-048) – serotonin 5-HT2A receptor antagonist Piromelatine (Neu-P11) – melatonin MT1 and MT2 receptor agonist, serotonin 5-HT1A and 5-HT1D receptor agonist, and serotonin 5-HT2B receptor antagonist Seltorexant (JNJ-42847922; JNJ-7922; MIN-202) – orexin OX2 receptor antagonist Sunobinop (IMB-115; IT-1315; RSC117957; S-117957; V-117957) – nociceptin receptor agonist 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

Phase 1/2 SVT-4A1011 – microbiome modulator and live microbial therapeutic

Phase 1 Ramelteon controlled-release – melatonin MT1 and MT2 receptor agonist

Preclinical APSTZD (APS-TZD) – undefined mechanism of action HS-10506 – orexin OX2 receptor antagonist TPT-0601 – fatty acid amide hydrolase (FAAH) inhibitor YZG-331 – adenosine receptor agonist

Research Trazodone (TrazoFlex-24; TrazoFlex-CR; TrazoFlex) – 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

Phase unknown Midazolam sublingual film – GABAA receptor positive allosteric modulator and benzodiazepine OP-010 (OP010) – undefined mechanism of action Zolpidem extended-release – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug

Not under development Suspended Osemozotan (MKC-242; MN-305) – serotonin 5-HT1A receptor agonist

No development reported Filorexant (MK-6096) – orexin OX1 and OX2 receptor antagonist HEC-83518 – orexin receptor antagonist IN-AQUL-001 – undefined mechanism of action JNJ-48816274 – orexin OX2 receptor antagonist Lirequinil (RO-413696) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/benzoquinolizinone Lorediplon (GF-015535-00) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine MK-1064 – orexin OX2 receptor antagonist Research programme: psychophysiological insomnia therapeutics - Neurim Pharmaceuticals – melatonin and serotonin receptor agonists Zolpidem topical gel (TR-396) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug

Discontinued ACT-462206 – orexin OX1 and OX2 receptor antagonist Adipiplon (NG-273) – GABAA receptor positive allosteric modulator ADX-10061 (NNC 01-0687; CEE-03-310; NNC-687) – dopamine D1 receptor antagonist Almorexant (ACT-078573) – orexin OX1 and OX2 receptor antagonist ANPH-101 – undefined mechanism of action Atagabalin (PD-0200390) – gabapentinoid (α2δ voltage-gated calcium channel ligand) Eplivanserin (Ciltyri; Sliwens; SR–46349; SR–46349B; SR–46615A) – serotonin 5-HT2A receptor antagonist Esmirtazapine (ORG-50081; SCH-900265; (S)-mirtazapine) – histamine H1 receptor antagonist, serotonin 5-HT2 receptor antagonist, and α2-adrenergic receptor antagonist Gaboxadol (LU-02030; LU-2-030; MK-0928; OV-101; THIP) – GABAA receptor agonist GT-2203 – histamine H3 receptor agonist Indiplon (NBI-34060) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine LY-2624803 (HY-10275) – histamine H1 receptor inverse agonist and serotonin 5-HT2A receptor antagonist Nabilone (Cesamet) – cannabinoid CB1 and CB2 receptor agonist NBI-75043 – antihistamine (histamine H1 receptor antagonist) Nelotanserin (APD-125; RVT-102) – serotonin 5-HT2A receptor antagonist NGD-962 (NGD 96-2) – GABAA receptor modulator Paliperidone (Invega; JNS-007ER; RO-76477; 9-hydroxyrisperidone) – atypical antipsychotic (non-selective monoamine receptor modulator) PD-0299685 (PF-299685) – gabapentinoid (α2δ voltage-gated calcium channel ligand) Pruvanserin (EMD-281014; LY-2422347; LSN-2411347) – serotonin 5-HT2A receptor antagonist Remimazolam (HR-7056; Byfavo) – GABAA receptor positive allosteric modulator and benzodiazepine Seganserin (R-56413) – serotonin 5-HT2A and 5-HT2C receptor antagonist Suvecaltamide (CX-8998; JZP-385; MK-8998) – T-type calcium channel inhibitor Tasipimidine (ODM-105) – α2A-adrenergic receptor agonist Tesamorelin (Egrifta; MDVTM; TH-9507; ThGRF 1-44) – growth hormone-releasing hormone (GHRH) receptor agonist Tiagabine (A-70569; CEP-6671; Gabitril; NO-050328; NO-328) – GABA transporter 1 (GAT-1) blocker and GABA reuptake inhibitor Triazolam intranasal (Hypnostat; TGAR01H) – GABAA receptor positive allosteric modulator and benzodiazepine Volinanserin (M-100907; MDL-100907) – serotonin 5-HT2A receptor antagonist

Formal development never or not yet started Histone deacetylase inhibitors (HDACi) (e.g., butyric acid (butyrate), tributyrin)

Clinically used drugs Approved drugs GABAA receptor positive allosteric modulators Benzodiazepines

Dimdazenil (Junoenil; EVT-201) – GABAA receptor partial positive allosteric modulator and benzodiazepine Quazepam (Doral; SCH-16134) – GABAA receptor positive allosteric modulator and benzodiazepine Other benzodiazepines (GABAA receptor positive allosteric modulators) (e.g., estazolam, flurazepam, temazepam, triazolam, others)

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 Zaleplon (Sonata; Zerene; CL–284846; L–846; LJC–10846) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug Zolpidem extended-release (Ambien CR; FK-199B; Stilnox; Zolpidem XR) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug Zolpidem oral spray (Zolpimist) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug Zolpidem sublingual (Edluar; Sublinox; OX-22) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug

Orexin receptor antagonists Daridorexant (Quviviq; ACT-541468; nemorexant) – orexin OX1 and OX2 receptor antagonist Fazamorexant (Mengping; HY-901139; YZJ-1139) – orexin OX1 and OX2 receptor antagonist Lemborexant (Dayvigo; E-2006) – orexin OX1 and OX2 receptor antagonist Suvorexant (Belsomra; MK-4305) – orexin OX1 and OX2 receptor antagonist Vornorexant (Vorzzz; ORN-0829; TS-142) – orexin OX1 and OX2 receptor antagonist

Melatonin receptor agonists Melatonin controlled-release (Circadin; Orlogin; PedPRM; Slenyto; KI-1001) – melatonin MT1 and MT2 receptor agonist Ramelteon (Rozerem; TAK-375) – melatonin MT1 and MT2 receptor agonist

Other drugs Doxepin low dose (Silenor; SO-101) – antihistamine (histamine H1 receptor antagonist) 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)

Withdrawn drugs GABAA receptor positive allosteric modulators Zolpidem sublingual (Intermezzo) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug

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) α2-Adrenergic receptor agonists (e.g., clonidine, tizanidine) Agomelatine (Valdoxan, Thymanax) – melatonin MT1 and MT2 receptor agonist and weak serotonin 5-HT2C receptor antagonist Amanita muscaria or muscimol – GABAA receptor agonist Antihistamines (histamine H1 receptor antagonists) (e.g., diphenhydramine, doxylamine, hydroxyzine, cyproheptadine, promethazine) Atypical antipsychotics (e.g., quetiapine, olanzapine, risperidone) Cannabinoids (cannabinoid receptor modulators) (e.g., cannabis, dronabinol/tetrahydrocannabinol (THC), cannabidiol (CBD)) Gabapentinoids (α2δ voltage-gated calcium channel ligands) (e.g., gabapentin, pregabalin, gabapentin enacarbil) 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) Serotonin precursors (indirect serotonin receptor agonists) (e.g., tryptophan, 5-HTP) Tetracyclic antidepressants (TeCAs) (e.g., mirtazapine) 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 Tricyclic antidepressants (TCAs) (e.g., amitriptyline, high-dose doxepin, trimipramine)

See also List of investigational drugs List of investigational narcolepsy and hypersomnia drugs List of investigational chronobiotics Hypnotic

References

External links AdisInsight - Springer