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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H21FN2O
Molecular Weight 348.4142
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SARIZOTAN

SMILES

c1ccc2c(c1)CC[C@]([H])(CNCc3cc(cnc3)-c4ccc(cc4)F)O2

InChI

InChIKey=HKFMQJUJWSFOLY-OAQYLSRUSA-N
InChI=1S/C22H21FN2O/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/t21-/m1/s1

HIDE SMILES / InChI

Molecular Formula C22H21FN2O
Molecular Weight 348.4142
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Gateways to clinical trials.
2003 May
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
Effects of sarizotan on the corticostriatal glutamate pathways.
2005 Dec 1
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
Investigation of sarizotan's impact on the pharmacokinetics of probe drugs for major cytochrome P450 isoenzymes: a combined cocktail trial.
2006 Apr
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
The effect of chronic administration of sarizotan, 5-HT1A agonist/D3/D4 ligand, on haloperidol-induced repetitive jaw movements in rat model of tardive dyskinesia.
2006 Mar
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
The novel antidyskinetic drug sarizotan elicits different functional responses at human D2-like dopamine receptors.
2006 Sep
Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties.
2006 Sep
Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.
2007 Jan 15
[Dyskinesia in Parkinson's disease--major clinical features, aetiology, therapy].
2007 Jul
Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.
2007 May
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 Sat Jun 26 11:53:54 UTC 2021
Edited
by admin
on Sat Jun 26 11:53:54 UTC 2021
Record UNII
467LU0UCUW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SARIZOTAN
INN   MI   WHO-DD  
INN  
Official Name English
3-PYRIDINEMETHANAMINE, 5-(4-FLUOROPHENYL)-N-(((2R)-3,4,4A,8A-TETRAHYDRO-2H-1-BENZOPYRAN-2-YL)METHYL)-
Common Name English
SARIZOTAN [MI]
Common Name English
EMD-77697
Code English
3-PYRIDINEMETHANAMINE, N-(((2R)-3,4-DIHYDRO-2H-1-BENZOPYRAN-2-YL)METHYL)-5-(4-FLUOROPHENYL)-
Systematic Name English
SARIZOTAN [INN]
Common Name English
1-(5-(4-FLUOROPHENYL)PYRIDIN-3-YL)-N-((2R)-3,4,4A,8A-TETRAHYDRO-2H-CHROMEN-2-YLMETHYL)METHANAMINE
Common Name English
SARIZOTAN [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 484015
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
NCI_THESAURUS C1509
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL220808
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY
INN
7748
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY
NCI_THESAURUS
C77567
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY
CAS
351862-32-3
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY
MESH
C443959
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY
DRUG BANK
DB06454
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY
PUBCHEM
6918388
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY
MERCK INDEX
M9782
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY Merck Index
FDA UNII
467LU0UCUW
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY
EVMPD
SUB04329MIG
Created by admin on Sat Jun 26 11:53:55 UTC 2021 , Edited by admin on Sat Jun 26 11:53:55 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
MAJOR
METABOLITE -> PARENT
to be confirm by NMR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC