SARIZOTAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H21FN2O
Molecular Weight	348.4133
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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	348.4133
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.businesswire.com/news/home/20150714005335/en/Newron-Receives-FDA-Orphan-Drug-Designation-Sarizotan | http://www.pharmatimes.com/news/merck_drops_late-stage_parkinsons_drug_996337 | https://clinicaltrials.gov/ct2/show/NCT02790034

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.

Originator

Approval Year

PubMed

Title	Date	PubMed
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	12236624
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	14614949
Gateways to clinical trials.	2003 May	12808477
Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile.	2004 Feb	14767715
Drugs in development for Parkinson's disease.	2004 Jul	15298067
Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study).	2004 Mar-Apr	15252265
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	15996562
Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease.	2005 Aug	15791634
Effects of sarizotan on the corticostriatal glutamate pathways.	2005 Dec 1	16138317
Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers.	2005 Jul	15717211
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	15987834
Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia.	2005 Sep	15707540
Investigation of sarizotan's impact on the pharmacokinetics of probe drugs for major cytochrome P450 isoenzymes: a combined cocktail trial.	2006 Apr	16525816
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	16959959
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	16229932
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	16874752
In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles.	2006 Sep	16947046
The novel antidyskinetic drug sarizotan elicits different functional responses at human D2-like dopamine receptors.	2006 Sep	16844149
Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties.	2006 Sep	16237379
Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.	2007 Jan 15	17094088
[Dyskinesia in Parkinson's disease--major clinical features, aetiology, therapy].	2007 Jul	17443441
Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats.	2007 Jul	17393144
Differential agonist and inverse agonist profile of antipsychotics at D2L receptors coupled to GIRK potassium channels.	2007 Mar	17239906
Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.	2007 May	17542349
Differential profile of typical, atypical and third generation antipsychotics at human 5-HT7a receptors coupled to adenylyl cyclase: detection of agonist and inverse agonist properties.	2007 Oct	17786406
Investigation of the impact of sarizotan on the pharmacokinetics of levodopa.	2007 Oct	17654694
Placebo influences on dyskinesia in Parkinson's disease.	2008 Apr 15	18175337
Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells.	2008 Feb 26	18190908
Effects of antipsychotics and reference monoaminergic ligands on marble burying behavior in mice.	2008 Mar	18332679
Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys.	2009 Jul	19196540
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	20219851
Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity.	2010 Nov 16	21103359
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	21591752

Patents

Sample Use Guides

In Vivo Use Guide

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 16 18:58:43 UTC 2022` Edited by `admin` on `Fri Dec 16 18:58:43 UTC 2022`
Record UNII	467LU0UCUW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SARIZOTAN

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 [WHO-DD]

Common 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

Classification Tree Code System Code

FDA ORPHAN DRUG

484015