RITANSERIN

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H25F2N3OS
Molecular Weight	477.569
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(CCN2CCC(CC2)=C(C3=CC=C(F)C=C3)C4=CC=C(F)C=C4)C(=O)N5C=CSC5=N1

InChI

InChIKey=JUQLTPCYUFPYKE-UHFFFAOYSA-N

InChI=1S/C27H25F2N3OS/c1-18-24(26(33)32-16-17-34-27(32)30-18)12-15-31-13-10-21(11-14-31)25(19-2-6-22(28)7-3-19)20-4-8-23(29)9-5-20/h2-9,16-17H,10-15H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10069551
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8974378 | https://www.ncbi.nlm.nih.gov/pubmed/3109453 | http://onlinelibrary.wiley.com/doi/10.1002/ddr.430250106/pdf | https://www.ncbi.nlm.nih.gov/pubmed/11141696 | https://www.ncbi.nlm.nih.gov/pubmed/18801405

Ritanserin (INN, USAN, BAN) is a serotonin receptor antagonist which was never marketed for clinical use but has been used in scientific research. In humans, ritanserin increases deep slow-wave sleep, improved liveliness in a variety of psychiatric disorders and facilitated participation in behaviour therapy. During clinical trials, unexpected observations indicated that ritanserin may be of value in treating obsessive-compulsive disorder, acute mania, negative symptoms of schizophrenia, drug addicts, etc. Clinical observations confirmed the efficacy of ritanserin in the chronic withdrawal phase after detoxification from ethanol. Ritanserin had been in phase III clinical trials by Janssen L.P. for the treatment of anxiety disorder and major depressive disorder. However, the clinical development of ritanserin was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 1a (5-HT1a) receptor 177 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19754201	Antagonist 2849	251.2 nM [Kd]
Serotonin 2c (5-HT2c) receptor 131 Target ID: CHEMBL225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18282705	Antagonist 2849	1.8 nM [Ki]
Serotonin 7 (5-HT7) receptor 30 Target ID: CHEMBL3155 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12825922	Antagonist 2849	45.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Cushing’s disease 13 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11141696	Primary	Not Provided 511	Unknown Approved Use Unknown
Negative symptoms of schizophrenia 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18801405	Primary	Not Provided 511	Unknown Approved Use Unknown
Acute mania 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12816549	Primary	Not Provided 511	Unknown Approved Use Unknown
Cocaine-related disorders 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00000187	Primary	Phase II 1147	Unknown Approved Use Unknown
Narcolepsy 20 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12905101	Primary	Not Provided 511	Unknown Approved Use Unknown
Alcohol addiction 24 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10069551	Primary	Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
73.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1910052	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		RITANSERIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
121 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/1910052	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		RITANSERIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
2031 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1910052	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		RITANSERIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
3867 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/1910052	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		RITANSERIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
39.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1910052	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		RITANSERIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
41 h REVIEW https://pubmed.ncbi.nlm.nih.gov/1910052	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		RITANSERIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY115039	https://www.001chemical.com/chem/search?q=DY115039
1PlusChem LLC	1P008E6B	https://www.1pchem.com/search?query=1P008E6B
AK Scientific	3726AC	https://aksci.com/item_detail.php?cat=3726AC
ApexBio Technology	B6898	https://www.apexbt.com/catalogsearch/result/?q=B6898
AstaTech	55492	http://astatechinc.com/CPSResult.php?CRNO=55492
BLD Pharm	BD150457	http://www.bldpharm.com/search/Search.html?keyword=BD150457
BOC Sciences	87051-43-2	http://www.bocsci.com/description.asp?cas=87051-43-2
Cayman Chemical	21374	http://www.caymanchem.com/app/template/Product.vm/catalog/21374
Chem Scene	CS-0002823	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0002823
ChemShuttle	105099	https://www.chemshuttle.com/catalogsearch/result/?q=105099
eMolecules	594025	https://orderbb.emolecules.com/search/#?query=594025
eNovation Chemicals	D381321	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D381321&searchbtn.x=0&searchbtn.y=0
Matrix Scientific	98269	http://www.matrixscientific.com/098269.html
mcule	MCULE-1911638043	https://mcule.com/MCULE-1911638043/
mcule	MCULE-9424377828	https://mcule.com/MCULE-9424377828/
MedChem Express	HY-10791	https://www.medchemexpress.com/search.html?q=HY-10791&ft=&fa=&fp=
Molcore	MC115039	http://www.molcore.com/CatMC115039.html
MolPort	MolPort-003-666-486	https://www.molport.com/shop/molecule-link/MolPort-003-666-486
MuseChem	R049212	https://www.musechem.com/product/R049212.html
ShangHai Biochempartner	BCP13728	http://www.biochempartner.com/search_BCP13728
Tetrahedron	TS72361	http://www.thsci.com/search.do?q=TS72361
Tocris	1955	https://www.tocris.com/search.php?Type=QuickSearch&Value=1955

PubMed

Title	Date	PubMed
Presynaptic modulation of rat arterial chemoreceptor function by 5-HT: role of K+ channel inhibition via protein kinase C.	2003-09-15	12826651
Mirtazapine in L-dopa-induced dyskinesias.	2003-08-05	12897636
Evidence that central 5-HT2A and 5-HT2B/C receptors regulate 5-HT cell firing in the dorsal raphe nucleus of the anaesthetised rat.	2003-07	12839874
Risperidone attenuates the discriminative-stimulus effects of d-amphetamine in humans.	2003-07	12676890
Ritanserin as an adjunct to lithium and haloperidol for the treatment of medication-naive patients with acute mania: a double blind and placebo controlled trial.	2003-06-19	12816549
Insurmountable antagonism of AT-1015, a 5-HT2 antagonist, on serotonin-induced endothelium-dependent relaxation in porcine coronary artery.	2003-06	12841944
Efficacy of low-dose mirtazapine in neuroleptic-induced akathisia: a double-blind randomized placebo-controlled pilot study.	2003-06	12826992
Functional study of rat 5-HT2A receptors using antisense oligonucleotides.	2003-06	12753068
A 5-HT1A agonist and a 5-HT2c antagonist reduce social interaction deficit induced by multiple ethanol withdrawals in rats.	2003-06	12677355
5-HT2 and 3 receptor antagonists suppress the response of rat type I slowly adapting mechanoreceptor: an in vitro study.	2003-04-18	12676383
Pharmacological characterization of an adenylyl cyclase-coupled 5-HT receptor in aplysia: comparison with mammalian 5-HT receptors.	2003-03	12611939
Ketanserin stabilizes blood pressure in conscious spontaneously hypertensive rats.	2003-03	12603350
Localization of serotonin and its possible role in early embryos of Tritonia diomedea(Mollusca: Nudibranchia).	2003-02	12596045
Characterization of the 5-hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureter.	2003-01	12522083
Evidence that the anorexia induced by lipopolysaccharide is mediated by the 5-HT2C receptor.	2003-01	12479973
Further evidence that the discriminative stimulus properties of indorenate are mediated by 5-HT 1A/1B/2C receptors.	2003-01	12479957
Anxiolytic effect of ting-chih-wan in mouse behavior models of anxiety.	2003	12723754
Dopamine and serotonin receptors mediating contractions of the snail, Helix pomatia, salivary duct.	2003	12573719
Excitation by dopamine of rat subthalamic nucleus neurones in vitro-a direct action with unconventional pharmacology.	2003	12535949
Benefits and risks of pharmacotherapy for dysthymia: a systematic appraisal of the evidence.	2003	12495364
Functional cooperation between neurosteroids and D2 dopamine antagonists on KCl-evoked [3H]noradrenaline release: modulation by calcium channel blockers.	2002-12	12472876
Smooth muscle 5-HT2A receptors mediating contraction of porcine isolated proximal stomach strips.	2002-12	12466231
Hypotension caused by extracorporeal circulation: serotonin from pump-activated platelets triggers nitric oxide release.	2002-11-12	12427656
Involvement of 5-HT7 receptors in serotonergic effects on spike afterpotentials in presumed jaw-closing motoneurons of rats.	2002-11-08	12414103
Differential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration.	2002-11-01	12393228
Prenatal opiate withdrawal activates the chick embryo hypothalamic pituitary-adrenal axis and dilates vitelline blood vessels via serotonin(2) receptors.	2002-10	12235259
Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigs.	2002-09-27	12231467
Effects of sarpogrelate, a novel 5-HT2 antagonist, on 5-HT-induced endothelium-dependent relaxations in porcine coronary artery.	2002-08	12233819
Vasodilator and vasoconstrictor responses induced by 5-hydroxytryptamine in the in situ blood autoperfused hindquarters of the anaesthetized rat.	2002-08	12122496
Acute and long-term effects of the 5-HT2 receptor antagonist ritanserin on EEG power spectra, motor activity, and sleep: changes at the light-dark phase shift.	2002-07-05	12088844
5-HT2A and 5-HT2C serotonin receptors differentially modulate mouse sexual arousal and the hypothalamo-pituitary-testicular response to the presence of a female.	2002-07	12097814
Erratum to "CNS drugs in Cushing's disease: pathophysiological and therapeutic implications for mood disorders" [Prog. Neuro-Psycol. Biol. Psychiatry, 26, 763 (2002)].	2002-06	12369251
Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms.	2002-06	12107618
Recent advances in 5-HT1B/1D receptor antagonists and agonists and their potential therapeutic applications.	2002-06	12052194
Decrease of core body temperature in mice by dehydroepiandrosterone.	2002-06	12037127
Residual symptoms in depression an emerging therapeutic concept.	2002-05	12188108
Nefazodone treatment of dysthymic disorder an open, long-term, prospective pilot study.	2002-05	12188098
Modulation by 5-hT2A receptors of aggressive behavior in isolated mice.	2002-05	12083749
Peripheral 5-HT(2A)-receptor-mediated formation of an inhibitor of atrial natriuretic peptide binding involves inflammation.	2002-04-05	11959086
Role of central 5-HT(2) receptors in fluoxetine-induced decreases in T lymphocyte activity.	2002-04	11908920
Effect of SB-243213, a selective 5-HT(2C) receptor antagonist, on the rat sleep profile: a comparison to paroxetine.	2002-04	11888551
Specific labelling of serotonin 5-HT(1B) receptors in rat frontal cortex with the novel, phenylpiperazine derivative, [3H]GR125,743. A pharmacological characterization.	2002-04	11888550
Modulation of cannabinoid agonist binding by 5-HT in the rat cerebellum.	2002-03	11953460
The human 5-HT7 serotonin receptor splice variants: constitutive activity and inverse agonist effects.	2002-03	11906971
The atypical 5-HT2 receptor mediating tachycardia in pithed rats: pharmacological correlation with the 5-HT2A receptor subtype.	2002-03	11906967
Ritanserin, a serotonin-2 receptor antagonist, improves ultradian sleep rhythmicity in young poor sleepers.	2002-03	11897543
5-HT(1B) but not 5-HT(6) or 5-HT(7) receptors mediate depression of spinal nociceptive reflexes in vitro.	2002-02	11861321
m-CPP hypolocomotion is selectively antagonized by compounds with high affinity for 5-HT(2C) receptors but not 5-HT(2A) or 5-HT(2B) receptors.	2001-12	11856898
Assessment of affinity and dissociation ability of a newly synthesized 5-HT2 antagonist, AT-1015: comparison with other 5-HT2 antagonists.	2001-11	11885967
The effect of Psilocybe cubensis extract on hippocampal neurons in vitro.	2001	11962085

Patents

Sample Use Guides

In Vivo Use Guide

2.5 mg, 5 mg or 10 mg ritanserin given once daily over 6 months

Route of Administration: Oral

In Vitro Use Guide

HeLa and human glioblastoma cells, U87 and U251, were treated as follows: 4 and 40 mkM of R59022 and ritanserin, 40 mkM ketanserin, and 100 nM PMA for 30 min with and without pretreatment with 500 nM bisindolylmaleimide II for 1 h. For additional PKC activation experiments, HeLa cells were treated with 10 mkM TCB-2 for 6 h with and without co-treatment with 40 mkM ketanserin, 40 mkM ketanserin alone, and 500 nM bisindolylmaleimide II for 1 h. The cells were lysed in IPBB, 20 mM Tris-HCl pH 7.5, 150 mM NaCl, 1% Triton X-100 and protease inhibitors and the cell lysate was cleared by centrifugation at 16,000g for 10 min.

Name

Type

Language

TISERTON

Preferred Name

English

RITANSERIN

Official Name

English

ritanserin [INN]

Common Name

English

5H-THIAZOLO(3,2-A)PYRIMIDIN-5-ONE, 6-(2-(4-BIS(4-FLUOROPHENYL)METHYLENE)-1-PIPERIDINYL)ETHYL)-7-METHYL-

Common Name

English

Ritanserin [WHO-DD]

Common Name

English

RITANSERIN [MART.]

Common Name

English

R-55667

Code

English

NSC-758470

Code

English

RITANSERIN [USAN]

Common Name

English

RITANSERIN [VANDF]

Common Name

English

6-(2-(4-(BIS(P-FLUOROPHENYL)METHYLENE)-PIPERIDINO)ETHYL)-7-METHYL-5H-THIAZOLO-(3,2-A)PYRIMIDIN-5-ONE

Common Name

English

R 55,667

Code

English

RITANSERIN [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66885