RITANSERIN

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

Molecular Formula	C27H25F2N3OS
Molecular Weight	477.569
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 172 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19754201	Antagonist 2778	251.2 nM [Kd]
Serotonin 2c (5-HT2c) receptor 124 Target ID: CHEMBL225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18282705	Antagonist 2778	1.8 nM [Ki]
Serotonin 7 (5-HT7) receptor 31 Target ID: CHEMBL3155 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12825922	Antagonist 2778	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 504	Unknown Approved Use Unknown
Negative symptoms of schizophrenia 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18801405	Primary	Not Provided 504	Unknown Approved Use Unknown
Acute mania 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12816549	Primary	Not Provided 504	Unknown Approved Use Unknown
Cocaine-related disorders 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00000187	Primary	Phase II 1132	Unknown Approved Use Unknown
Narcolepsy 20 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12905101	Primary	Not Provided 504	Unknown Approved Use Unknown
Alcohol addiction 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10069551	Primary	Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

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
Matrix Scientific	98269	http://www.matrixscientific.com/098269.html
MedChem Express	HY-10791	https://www.medchemexpress.com/search.html?q=HY-10791&ft=&fa=&fp=
MolPort	MolPort-003-666-486	https://www.molport.com/shop/molecule-link/MolPort-003-666-486
Molcore	MC115039	http://www.molcore.com/CatMC115039.html
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
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
mcule	MCULE-1911638043	https://mcule.com/MCULE-1911638043/
mcule	MCULE-9424377828	https://mcule.com/MCULE-9424377828/

PubMed

Title	Date	PubMed
5-HT2 receptor antagonism reduces hyperactivity induced by amphetamine, cocaine, and MK-801 but not D1 agonist C-APB.	1999 Jun	10371652
Differential modes of agonist binding to 5-hydroxytryptamine(2A) serotonin receptors revealed by mutation and molecular modeling of conserved residues in transmembrane region 5.	2000 Nov	11040033
Expression of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors in the mouse embryo.	2000 Nov	10978843
Effects of the serotonin 5-HT(2) antagonist, ritanserin, and the serotonin 5-HT(1A) antagonist, WAY 100635, on cocaine-seeking in rats.	2000 Oct	11124402
The effect of Psilocybe cubensis extract on hippocampal neurons in vitro.	2001	11962085
The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea.	2001	11686898
Neonatal dopamine depletion reveals a synergistic mechanism of mRNA regulation that is mediated by dopamine(D1) and serotonin(2) receptors and is targeted to tachykinin neurons of the dorsomedial striatum.	2001	11516832
New developments in the pharmacotherapy of alcohol dependence.	2001	11268820
A 5-HT(7) receptor-mediated depolarization in the anterodorsal thalamus. I. Pharmacological characterization.	2001 Apr	11259568
Cataleptic effect of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in mice: modulation by serotonergic agents.	2001 Apr 13	11292445
Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution.	2001 Apr 27	11343685
Fenfluramine-induced pulmonary vasoconstriction: role of serotonin receptors and potassium channels.	2001 Aug	11457791
Serotonin 2A receptor regulation of striatal neuropeptide gene expression is selective for tachykinin, but not enkephalin neurons following dopamine depletion.	2001 Aug 15	11483243
Serotonin localization in Phallusia mammillata larvae and effects of 5-HT antagonists during larval development.	2001 Dec	11737145
Serotonergic modulation of retinal input to the mouse suprachiasmatic nucleus mediated by 5-HT1B and 5-HT7 receptors.	2001 Feb	11220775
Endogenous 5-HT tonically inhibits spontaneous firing activity of dorsal hippocampus CA1 pyramidal neurons through stimulation of 5-HT(1A) receptors in quiet awake rats: in vivo electrophysiological evidence.	2001 Feb	11120396
The antidepressant activity of inositol in the forced swim test involves 5-HT(2) receptors.	2001 Jan 8	11163636
Serotonin-based pharmacotherapy for acute neuroleptic-induced akathisia: a new approach to an old problem.	2001 Jul	11435260
In vivo resetting of the hamster circadian clock by 5-HT7 receptors in the suprachiasmatic nucleus.	2001 Jul 15	11438611
Role of 5-HT(1A) and 5-HT(7) receptors in the facilitatory response induced by 8-OH-DPAT on learning consolidation.	2001 Jun	11275281
The GR127935-sensitive 5-HT(1) receptors mediating canine internal carotid vasoconstriction: resemblance to the 5-HT(1B), but not to the 5-HT(1D) or 5-ht(1F), receptor subtype.	2001 Mar	11226129
Evidence for 5-HT(1B/1D) and 5-HT(2A) receptors mediating constriction of the canine internal carotid circulation.	2001 Mar	11226128
Subchronic effects of the GABA-agonist lorazepam and the 5-HT2A/2C antagonist ritanserin on driving performance, slow wave sleep and daytime sleepiness in healthy volunteers.	2001 Mar 1	11314681
Embryonic cocaine exposure and corticosterone: serotonin(2) receptor mediation.	2001 May-Jun	11420070
Binding affinity of a newly synthesized 5-HT2 antagonist, AT-1015 (N-[2-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-piperidino]ethyl]-1-formyl-4-piperidinecarboxamide monohydrochloride monohydrate), in the rabbit platelet membrane.	2001 Oct	11642330
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.	2001 Oct	11561066
Embryonic "binge" cocaine exposure alters neural-immune and neural-endocrine interactions in young chickens: involvement of serotonin(2) receptors.	2001 Sep 23	11557098
Role of central 5-HT(2) receptors in fluoxetine-induced decreases in T lymphocyte activity.	2002 Apr	11908920
Peripheral 5-HT(2A)-receptor-mediated formation of an inhibitor of atrial natriuretic peptide binding involves inflammation.	2002 Apr 5	11959086
Effects of sarpogrelate, a novel 5-HT2 antagonist, on 5-HT-induced endothelium-dependent relaxations in porcine coronary artery.	2002 Aug	12233819
Vasodilator and vasoconstrictor responses induced by 5-hydroxytryptamine in the in situ blood autoperfused hindquarters of the anaesthetized rat.	2002 Aug	12122496
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 Jul	12097814
Recent advances in 5-HT1B/1D receptor antagonists and agonists and their potential therapeutic applications.	2002 Jun	12052194
Decrease of core body temperature in mice by dehydroepiandrosterone.	2002 Jun	12037127
Modulation of cannabinoid agonist binding by 5-HT in the rat cerebellum.	2002 Mar	11953460
Residual symptoms in depression an emerging therapeutic concept.	2002 May	12188108
Nefazodone treatment of dysthymic disorder an open, long-term, prospective pilot study.	2002 May	12188098
Modulation by 5-hT2A receptors of aggressive behavior in isolated mice.	2002 May	12083749
Involvement of 5-HT7 receptors in serotonergic effects on spike afterpotentials in presumed jaw-closing motoneurons of rats.	2002 Nov 8	12414103
Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigs.	2002 Sep 27	12231467
Localization of serotonin and its possible role in early embryos of Tritonia diomedea(Mollusca: Nudibranchia).	2003 Feb	12596045
Mirtazapine in L-dopa-induced dyskinesias.	2003 Jul-Aug	12897636
Insurmountable antagonism of AT-1015, a 5-HT2 antagonist, on serotonin-induced endothelium-dependent relaxation in porcine coronary artery.	2003 Jun	12841944
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 Jun 19	12816549
Pharmacological characterization of an adenylyl cyclase-coupled 5-HT receptor in aplysia: comparison with mammalian 5-HT receptors.	2003 Mar	12611939
Ketanserin stabilizes blood pressure in conscious spontaneously hypertensive rats.	2003 Mar	12603350
Presynaptic modulation of rat arterial chemoreceptor function by 5-HT: role of K+ channel inhibition via protein kinase C.	2003 Sep 15	12826651

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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:21:31 GMT 2023` Edited by `admin` on `Sat Dec 16 16:21:31 GMT 2023`
Record UNII	145TFV465S
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

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

TISERTON

Brand 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