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 It is likely to become outdated with time.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)
• Diphenhydramine/lorazepam/zolpidem (SM-1; SM1) – combination of diphenhydramine (antihistamine and anticholinergic), lorazepam (benzodiazepine and GABA_A receptor positive allosteric modulator), and zolpidem (nonbenzodiazepine/Z-drug and GABA_A receptor positive allosteric modulator)
• Fazamorexant (YZJ-1139) – orexin OX₁ and OX₂ receptor antagonist
• Vornorexant (ORN-0829; TS-142) – orexin OX₁ and OX₂ receptor antagonist
• Zuranolone (BIIB-125; S-812217; SAGE-217; SGE-797; Zurzuvae) – GABA_A receptor positive allosteric modulator and neurosteroid

Phase 2

• Lumateperone (Caplyta; ITI-007; ITI-722) – atypical antipsychotic (non-selective monoamine receptor modulator)
• Pimavanserin (Nuplazid; ACP-103; BVF-048) – serotonin 5-HT_2A receptor antagonist
• Piromelatine (Neu-P11) – melatonin MT₁ and MT₂ receptor agonist, serotonin 5-HT_1A and 5-HT_1D receptor agonist, and serotonin 5-HT_2B 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
• Tasipimidine (ODM-105) – α_2A-adrenergic receptor agonist
• Trazodone extended-release (AF-1161; DDS-04A; Oleptro; Triticum AC; Trittico) – serotonin 5-HT_1A receptor partial agonist, serotonin 5-HT_2A and 5-HT_2C 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

Preclinical

• TPT-0601 – fatty acid amide hydrolase (FAAH) inhibitor
• YZG-331 – adenosine receptor agonist

Not under development

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) – GABA_A receptor positive allosteric modulator and nonbenzodiazepine/benzoquinolizinone
• Lorediplon (GF-015535-00) – GABA_A 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) – GABA_A receptor positive allosteric modulator and nonbenzodiazepine/Z-drug

Discontinued

• ACT-462206 – orexin OX₁ and OX₂ receptor antagonist
• Adipiplon (NG-273) – GABA_A 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-HT_2A 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) – GABA_A receptor agonist
• GT-2203 – histamine H₃ receptor agonist
• Indiplon (NBI-34060) – GABA_A receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine
• LY-2624803 (HY-10275) – histamine H₁ receptor inverse agonist and serotonin 5-HT_2A receptor antagonist
• Nabilone (Cesamet) – cannabinoid CB₁ and CB₂ receptor agonist
• NBI-75043 – antihistamine (histamine H₁ receptor antagonist)
• Nelotanserin (APD-125; RVT-102) – serotonin 5-HT_2A receptor antagonist
• NGD-962 (NGD 96-2) – GABA_A 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-HT_2A receptor antagonist
• Remimazolam (HR-7056; Byfavo) – GABA_A receptor positive allosteric modulator and benzodiazepine
• Seganserin (R-56413) – serotonin 5-HT_2A and 5-HT_2C receptor antagonist
• Suvecaltamide (CX-8998; JZP-385; MK-8998) – T-type calcium channel inhibitor
• 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) – GABA_A receptor positive allosteric modulator and benzodiazepine
• Volinanserin (M-100907; MDL-100907) – serotonin 5-HT_2A receptor antagonist

Clinically used drugs

Approved drugs

GABA_A receptor positive allosteric modulators

Benzodiazepines

• Dimdazenil (Junoenil; EVT-201) – GABA_A receptor partial positive allosteric modulator and benzodiazepine
• Quazepam (Doral; SCH-16134) – GABA_A receptor positive allosteric modulator and benzodiazepine
• Other benzodiazepines (GABA_A 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) – GABA_A receptor positive allosteric modulator and nonbenzodiazepine/Z-drug
• Zaleplon (Sonata; Zerene; CL–284846; L–846; LJC–10846) – GABA_A receptor positive allosteric modulator and nonbenzodiazepine/Z-drug
• Zolpidem extended-release (Ambien CR; FK-199B; Stilnox; Zolpidem XR) – GABA_A receptor positive allosteric modulator and nonbenzodiazepine/Z-drug
• Zolpidem oral spray (Zolpimist) – GABA_A receptor positive allosteric modulator and nonbenzodiazepine/Z-drug

Orexin receptor antagonists

• Daridorexant (Quviviq; ACT-541468; nemorexant) – 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

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-HT_2A receptor antagonist and α₁-adrenergic receptor antagonist
• Phenibut (Anvifen) – GABA_B 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)

Discontinued drugs

GABA_A receptor positive allosteric modulators

• Barbiturates (e.g., amobarbital, pentobarbital, phenobarbital, secobarbital) – GABA_A receptor positive allosteric modulators
• Piperidinediones (e.g., glutethimide) – GABA_A receptor positive allosteric modulators
• Quinazolinones (e.g., methaqualone) – GABA_A 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)
• Agomelatine (Valdoxan, Thymanax) – melatonin MT₁ and MT₂ receptor agonist and weak serotonin 5-HT_2C receptor antagonist
• Amanita muscaria or muscimol – GABA_A 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 (GABA_A 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-HT_1A receptor partial agonist, serotonin 5-HT_2A and 5-HT_2C 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