Ritanserin

Overview

Ritanserin, also known by its developmental code name R-55667, is a serotonin receptor antagonist which was under development for the treatment of anxiety disorders and major depressive disorder but was never marketed. It was also investigated for treatment of insomnia, especially to enhance sleep quality by significantly increasing slow wave sleep by virtue of potent and concomitant serotonin 5-HT2A and 5-HT2C receptor antagonism. The drug is taken orally.[1–6] WP

Pharmacology

Pharmacodynamics

Ritanserin acts as a selective 5-HT2A (Kᵢ = 0.45 nM) and 5-HT2C receptor (Kᵢ = 0.71 nM) antagonist. It has relatively low affinity for the H₁, D₂, α₁-adrenergic, and α₂-adrenergic receptors (39-, 77-, 107-, and 166-fold lower relative to 5-HT2A, respectively). The affinity of ritanserin for the 5-HT1A receptor is less than 1 μM. In addition to its affinity for the 5-HT2A and 5-HT2C receptors, ritanserin also binds to and antagonizes the 5-HT1D, 5-HT2B, 5-HT5A, 5-HT₆, and 5-HT₇ receptors.[7][8][9] WP

Ritanserin blocks c-RAF activation and induces apoptotic cell death of non–small cell lung cancer and small cell lung cancer cells.[10] WP

Pharmacokinetics

The time to peak levels of ritanserin is 1.7 hours. Its elimination half-life is 54 hours.[11] WP

Research

Research

Ritanserin was tested in clinical trials for depression, anxiety, schizophrenia, and migraine. It was also found to improve sleep in human volunteers. It reached phase 3 clinical trials for major depressive disorder prior to the discontinuation of its development.[1][4][7][12][13] WP

Some of the safety liabilities that led to its discontinuation of ritanserin for treatment of insomnia have led to its potential repurposing in the field of oncology. Specifically, it acts as a potent inhibitor of diacylglycerol kinase alpha (DGKα). As such, it may be used to treat certain types of glioblastoma and melanoma. It has also been used as a reference compound to identify putatively more selective and potent DGKα inhibitors to treat these forms of cancer as well as possibly others.[14][15][16] WP

History

History

The atypical antipsychotic risperidone was developed via structural modification of ritanserin.[17] WP

Legal status

Names

Ritanserin is the generic name of the drug and its INN (International Nonproprietary Name), USAN (United States Adopted Name), and BAN (British Approved Name). It is also known by its developmental code name R-55667.[2][3] WP

Availability

Ritanserin was never approved or marketed for medical use.[13][18][19] WP

Chemistry

Formula

C27H25F2N3OS PC

CAS number

87051-43-2 PC

Molar mass (g/mol)

477.6 PC

IUPAC name (computed by PubChem)

6-[2-[4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl]ethyl]-7-methyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one PC

SMILES

CC1=C(C(=O)N2C=CSC2=N1)CCN3CCC(=C(C4=CC=C(C=C4)F)C5=CC=C(C=C5)F)CC3 PC

InChIKey

JUQLTPCYUFPYKE-UHFFFAOYSA-N PC

PubChem CID

5074

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Ritanserin. 7 January 1997
2. Other The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014
3. Other Morton I, Morton IK, Hall JM. Concise Dictionary of Pharmacological Agents: Properties and Synonyms. 31 October 1999
4. Other Handbook of Chronic Depression: Diagnosis and Therapeutic Management. 14 May 2014
5. Journal / agency Paiva T, Arriaga F, Wauquier A, Lara E, Largo R, Leitao JN. Effects of ritanserin on sleep disturbances of dysthymic patients. Psychopharmacology. 1988. doi:10.1007/BF00216069 · PMID 3146774
6. Journal / agency Idzikowski C, Mills FJ, Glennard R. 5-Hydroxytryptamine-2 antagonist increases human slow wave sleep. Brain Research. July 1986. doi:10.1016/0006-8993(86)90299-4 · PMID 3091188
7. Journal / agency Akhondzadeh S, Malek-Hosseini M, Ghoreishi A, Raznahan M, Rezazadeh SA. Effect of ritanserin, a 5HT2A/2C antagonist, on negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. Progress in Neuro-Psychopharmacology & Biological Psychiatry. December 2008. doi:10.1016/j.pnpbp.2008.08.020 · PMID 18801405
8. Journal / agency Leysen JE, Gommeren W, Van Gompel P, Wynants J, Janssen PF, Laduron PM. Receptor-binding properties in vitro and in vivo of ritanserin: A very potent and long acting serotonin-S2 antagonist. Molecular Pharmacology. June 1985. doi:10.1016/S0026-895X(25)12558-3 · PMID 2860558
9. Other Harmful Non-Indigenous Species in the United States. 1 February 1993
10. Journal / agency Campbell ST, Franks CE, Borne AL, Shin M, Zhang L, Hsu KL. Chemoproteomic Discovery of a Ritanserin-Targeted Kinase Network Mediating Apoptotic Cell Death of Lung Tumor Cells. Molecular Pharmacology. November 2018. doi:10.1124/mol.118.113001 · PMID 30158316 · PMC6160665
11. Journal / agency Barone JA, Bierman RH, Cornish JW, Hsuan A, Drake ND, Colaizzi JL. Safety evaluation of ritanserin--an investigational serotonin antagonist. Drug Intell Clin Pharm. October 1986. doi:10.1177/106002808602001006 · PMID 3095082
12. Journal / agency Nappi G, Sandrini G, Granella F, Ruiz L, Cerutti G, Facchinetti F, Blandini F, Manzoni GC. A new 5-HT2 antagonist (ritanserin) in the treatment of chronic headache with depression. A double-blind study vs amitriptyline. Headache. June 1990. doi:10.1111/j.1526-4610.1990.hed3007439.x · PMID 2119355
13. Journal / agency Atkin T, Comai S, Gobbi G. Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery. Pharmacological Reviews. April 2018. doi:10.1124/pr.117.014381 · PMID 29487083
14. Journal / agency Olmez I, Love S, Xiao A, Manigat L, Randolph P, McKenna BD, Neal BP, Boroda S, Li M, Brenneman B, Abounader R, Floyd D, Lee J, Nakano I, Godlewski J, Bronisz A, Sulman EP, Mayo M, Gioeli D, Weber M, Harris TE, Purow B. Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha. Neuro-Oncology. January 2018. doi:10.1093/neuonc/nox119 · PMID 29048560 · PMC5777487
15. Journal / agency Audia A, Bhat KP. Ritanserin, a novel agent targeting the mesenchymal subtype of glioblastomas. Neuro-Oncology. January 2018. doi:10.1093/neuonc/nox240 · PMID 29365204 · PMC5786216
16. Journal / agency Granade ME, Manigat LC, Lemke MC, Purow BW, Harris TE. Identification of ritanserin analogs that display DGK isoform specificity. Biochemical Pharmacology. March 2022. doi:10.1016/j.bcp.2022.114908 · PMID 34999054 · PMC8858877
17. Other Lowe III JA. Current Medicinal Chemistry. May 1994
18. Other Micromedex Products: Please Login
19. Other Swiss Pharmaceutical Society. Index Nominum 2000: International Drug Directory. 2000

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.