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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H21FN2O.ClH
Molecular Weight 384.874
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SARIZOTAN HYDROCHLORIDE

SMILES

Cl.FC1=CC=C(C=C1)C2=CN=CC(CNC[C@H]3CCC4=C(O3)C=CC=C4)=C2

InChI

InChIKey=QDLVYMYXOLGZOD-ZMBIFBSDSA-N
InChI=1S/C22H21FN2O.ClH/c23-20-8-5-17(6-9-20)19-11-16(12-24-14-19)13-25-15-21-10-7-18-3-1-2-4-22(18)26-21;/h1-6,8-9,11-12,14,21,25H,7,10,13,15H2;1H/t21-;/m1./s1

HIDE SMILES / InChI

Molecular Formula C22H21FN2O
Molecular Weight 348.4133
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Sarizotan (also known as EMD-128,130), a chromane derivative that was developed as a selective 5-HT1A receptor agonist and D2 receptor antagonist. Experiments on animal models have shown that the drug effectively suppressed levodopa-induced dyskinesia in primate and rodent models of Parkinson's disease, and tardive dyskinesia in a rodent model. Sarizotan participated in phase II/III clinical trials in the treatment of dyskinesia associated with the dopaminergic treatment of Parkinson's disease. However, further development for this disease was discontinued by Merk, because phase III did not confirm earlier Phase II findings. On July 14, 2015, Newron Pharmaceuticals, research, and development company focused on the novel central nervous system (CNS) and pain therapies, announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to sarizotan for treatment of Rett syndrome. Besides, the drug now is an ongoing clinical trial phase II/III to investigate its the tolerability and efficacy in reducing respiratory abnormalities in Rett Syndrome.

Approval Year

PubMed

PubMed

TitleDatePubMed
Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models.
2001 Nov 27
Evaluation of EMD 128 130 occupancy of the 5-HT1A and the D2 receptor: a human PET study with [11C]WAY-100635 and [11C]raclopride.
2002 Sep
Contribution of the serotonin 5-HT1A receptor agonism of 8-OH-DPAT and EMD 128130 to the regulation of haloperidol-induced muscle rigidity in rats.
2003 Dec
Gateways to clinical trials.
2003 May
Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile.
2004 Feb
Drugs in development for Parkinson's disease.
2004 Jul
Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study).
2004 Mar-Apr
Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats.
2005 Aug
Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease.
2005 Aug
Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers.
2005 Jul
Contrasting contribution of 5-hydroxytryptamine 1A receptor activation to neurochemical profile of novel antipsychotics: frontocortical dopamine and hippocampal serotonin release in rat brain.
2005 Oct
Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia.
2005 Sep
In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with\ increased motor disability.
2006 Dec
Translation of nondopaminergic treatments for levodopa-induced dyskinesia from MPTP-lesioned nonhuman primates to phase IIa clinical studies: keys to success and roads to failure.
2006 Oct
In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles.
2006 Sep
Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.
2007 Jan 15
Differential agonist and inverse agonist profile of antipsychotics at D2L receptors coupled to GIRK potassium channels.
2007 Mar
Placebo influences on dyskinesia in Parkinson's disease.
2008 Apr 15
Current approaches to the treatment of Parkinson's disease.
2008 Aug
Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells.
2008 Feb 26
Effects of antipsychotics and reference monoaminergic ligands on marble burying behavior in mice.
2008 Mar
Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys.
2009 Jul
In vitro characterization of sarizotan metabolism: hepatic clearance, identification and characterization of metabolites, drug-metabolizing enzyme identification, and evaluation of cytochrome p450 inhibition.
2010 Jun
Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity.
2010 Nov 16
Identification of N-propylnoraporphin-11-yl 5-(1,2-dithiolan-3-yl)pentanoate as a new anti-Parkinson's agent possessing a dopamine D2 and serotonin 5-HT1A dual-agonist profile.
2011 Jul 14
Patents

Patents

Sample Use Guides

Subjects will receive sarizotan 1 milligram orally twice daily for 24 weeks.
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:20:49 UTC 2023
Edited
by admin
on Fri Dec 15 17:20:49 UTC 2023
Record UNII
5P71E6YO9H
Record Status Validated (UNII)
Record Version
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Name Type Language
SARIZOTAN HYDROCHLORIDE
USAN  
USAN  
Official Name English
EMD-128130
Code English
3-PYRIDINEMETHANAMINE, N-(((2R)-3,4-DIHYDRO-2H-1-BENZOPYRAN-2-YL)METHYL)-5-(4-FLUOROPHENYL)-, MONOHYDROCHLORIDE
Common Name English
(-)-N-(((2R)-3,4-DIHYDRO-2H-1-BENZOPYRAN-2-YL)METHYL)-5-(4-FLUOROPHENYL)PYRIDINE-3-YL)METHANAMINE MONOHYDROCHLORIDE
Common Name English
SARIZOTAN HYDROCHLORIDE [USAN]
Common Name English
SARIZOTAN HCL
Common Name English
EMD 128130
Code English
3-PYRIDINEMETHANAMINE, N-(((2R)-3,4-DIHYDRO-2H-1-BENZOPYRAN-2-YL)METHYL)-5-(4-FLUOROPHENYL)-, HYDROCHLORIDE (1:1)
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1509
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
EU-Orphan Drug EU/3/15/1531
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
Code System Code Type Description
MESH
C443959
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
FDA UNII
5P71E6YO9H
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
NCI_THESAURUS
C76654
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
USAN
RR-123
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
ChEMBL
CHEMBL220808
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
SMS_ID
100000084888
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
CAS
195068-07-6
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
EPA CompTox
DTXSID60173163
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
EVMPD
SUB21592
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
PUBCHEM
6918387
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
DRUG BANK
DBSALT002015
Created by admin on Fri Dec 15 17:20:49 UTC 2023 , Edited by admin on Fri Dec 15 17:20:49 UTC 2023
PRIMARY
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