List of investigational chronobiotics
This is a list of investigational chronobiotics, or drugs that are currently under development for clinical use as chronobiotics—that is, for the treatment of circadian rhythm sleep disorders—but are not yet approved.
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 It is likely to become outdated with time.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
Phase 3
- Solriamfetol (ADX-N05; ARL-N05; JZP-110; SKL-N05; Sunosi) – norepinephrine–dopamine reuptake inhibitor (NDRI) and trace amine-associated receptor 1 (TAAR1) agonist[1]
Phase 2
- Lemborexant (LEM; Dayvigo; E-2006) – orexin OX1 and OX2 receptor antagonist[2]
Preclinical
Not under development
No development reported
- TIK-301 (LY-156735; PD-6735; 6-chloro-β-methylmelatonin) – melatonin MT1 and MT2 receptor agonist and serotonin 5-HT2B and 5-HT2C receptor antagonist[5]
Discontinued
- BIIB-118 (PF-5251749; PF-05251749) – casein kinase 1 epsilon (CK1ε) and delta (CK1δ) inhibitor[6]
- LML-134 (LML134) – histamine H3 receptor antagonist[7]
- Ramelteon (Rozerem; TAK-375) – melatonin MT1 and MT2 receptor agonist[8]
Clinically used drugs
Approved drugs
- Armodafinil (Nuvigil) – atypical dopamine reuptake inhibitor – specifically for shift work sleep disorder[9]
- Modafinil (Provigil) – atypical dopamine reuptake inhibitor – specifically for shift work sleep disorder[9][10][11]
- Tasimelteon (BMS-214778; Hetlioz; VEC-162) – melatonin MT1 and MT2 receptor agonist[12]
Off-label drugs
- Antipsychotics (e.g., aripiprazole)[13][14]
- Hypnotics (e.g., antihistamines, trazodone, orexin receptor antagonists, benzodiazepines, Z-drugs)[9][15]
- Melatonin receptor agonists (e.g., melatonin, ramelteon, agomelatine)[16]
- Vitamins (e.g., vitamin B12)[17]
- Wakefulness-promoting agents and stimulants (e.g., caffeine, modafinil, armodafinil)[18][19]
See also
- List of investigational drugs
- List of investigational insomnia drugs
- List of investigational narcolepsy and hypersomnia drugs
- Chronobiotic
References
- ^ "Solriamfetol - Jazz Pharmaceuticals/SK Biopharmaceuticals - AdisInsight".
- ^ "Lemborexant - Eisai - AdisInsight".
- ^ "CT 1500 - AdisInsight".
- ^ Jagannath A, Pretoro SD, Ebrahimjee F, Ftouni S, Taylor L, Foster RG, Vasudevan S (2022). "The regulation of circadian entrainment in mice by the adenosine the A 2A /A 1 receptor antagonist CT1500". Front Physiol. 13 1085217. doi:10.3389/fphys.2022.1085217. PMC 9808084. PMID 36605898.
- ^ "LY 156735 - AdisInsight".
- ^ "BIIB 118 - AdisInsight".
- ^ "LML 134 - AdisInsight".
- ^ "Ramelteon - Takeda - AdisInsight".
- ^ a b c Liira J, Verbeek JH, Costa G, Driscoll TR, Sallinen M, Isotalo LK, Ruotsalainen JH (August 2014). "Pharmacological interventions for sleepiness and sleep disturbances caused by shift work". Cochrane Database Syst Rev. 2014 (8) CD009776. doi:10.1002/14651858.CD009776.pub2. PMC 10025070. PMID 25113164.
- ^ Keating GM, Raffin MJ (2005). "Modafinil: a review of its use in excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder". CNS Drugs. 19 (9): 785–803. doi:10.2165/00023210-200519090-00005. PMID 16142993.
- ^ Kumar R (2008). "Approved and investigational uses of modafinil: an evidence-based review". Drugs. 68 (13): 1803–1839. doi:10.2165/00003495-200868130-00003. PMID 18729534.
- ^ "Tasimelteon - Vanda Pharmaceuticals - AdisInsight".
- ^ Takaki M, Ujike H (2014). "Aripiprazole is effective for treatment of delayed sleep phase syndrome". Clin Neuropharmacol. 37 (4): 123–124. doi:10.1097/WNF.0000000000000035. PMID 24992089.
- ^ Omori Y, Kanbayashi T, Sagawa Y, Imanishi A, Tsutsui K, Takahashi Y, Takeshima M, Takaki M, Nishino S, Shimizu T (2018). "Low dose of aripiprazole advanced sleep rhythm and reduced nocturnal sleep time in the patients with delayed sleep phase syndrome: an open-labeled clinical observation". Neuropsychiatr Dis Treat. 14: 1281–1286. doi:10.2147/NDT.S158865. PMC 5965391. PMID 29849459.
- ^ Spiegelhalder K, Nissen C, Riemann D (2019). "Clinical Sleep-Wake Disorders II: Focus on Insomnia and Circadian Rhythm Sleep Disorders". Handb Exp Pharmacol. Handbook of Experimental Pharmacology. 253: 261–276. doi:10.1007/164_2017_40. ISBN 978-3-030-11270-7. PMID 28707143.
- ^ Williams WP, McLin DE, Dressman MA, Neubauer DN (September 2016). "Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders". Pharmacotherapy. 36 (9): 1028–1041. doi:10.1002/phar.1822. PMC 5108473. PMID 27500861.
- ^ Morgenthaler TI, Lee-Chiong T, Alessi C, Friedman L, Aurora RN, Boehlecke B, Brown T, Chesson AL, Kapur V, Maganti R, Owens J, Pancer J, Swick TJ, Zak R (November 2007). "Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report". Sleep. 30 (11): 1445–1459. doi:10.1093/sleep/30.11.1445. PMC 2082098. PMID 18041479.
- ^ Morgenthaler, Timothy; Kolla; Auger (2012). "Circadian rhythm sleep disorders". ChronoPhysiology and Therapy: 19. doi:10.2147/CPT.S21937. ISSN 2230-2026.
- ^ Abbott SM, Reid KJ, Zee PC (December 2015). "Circadian Rhythm Sleep-Wake Disorders". Psychiatr Clin North Am. 38 (4): 805–823. doi:10.1016/j.psc.2015.07.012. PMID 26600110.