Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C22H21FN2O.2ClH |
| Molecular Weight | 421.335 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.FC1=CC=C(C=C1)C2=CN=CC(CNC[C@H]3CCC4=CC=CC=C4O3)=C2
InChI
InChIKey=ANXOJXYTTDGHAJ-GHVWMZMZSA-N
InChI=1S/C22H21FN2O.2ClH/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;2*1H/t21-;;/m1../s1
| 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 |
| 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 |
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
| Title | Date | PubMed |
|---|---|---|
| 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. | 2011-07-14 |
|
| Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity. | 2010-11-16 |
|
| In vitro characterization of sarizotan metabolism: hepatic clearance, identification and characterization of metabolites, drug-metabolizing enzyme identification, and evaluation of cytochrome p450 inhibition. | 2010-06 |
|
| Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys. | 2009-07 |
|
| Local administration of sarizotan into the subthalamic nucleus attenuates levodopa-induced dyskinesias in 6-OHDA-lesioned rats. | 2009-06 |
|
| Current approaches to the treatment of Parkinson's disease. | 2008-08 |
|
| Placebo influences on dyskinesia in Parkinson's disease. | 2008-04-15 |
|
| Effects of antipsychotics and reference monoaminergic ligands on marble burying behavior in mice. | 2008-03 |
|
| Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells. | 2008-02-26 |
|
| 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. | 2007-10 |
|
| Investigation of the impact of sarizotan on the pharmacokinetics of levodopa. | 2007-10 |
|
| [Dyskinesia in Parkinson's disease--major clinical features, aetiology, therapy]. | 2007-07 |
|
| 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. | 2007-07 |
|
| Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects. | 2007-05 |
|
| Differential agonist and inverse agonist profile of antipsychotics at D2L receptors coupled to GIRK potassium channels. | 2007-03 |
|
| Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial. | 2007-01-15 |
|
| 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. | 2006-12 |
|
| 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. | 2006-10 |
|
| In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles. | 2006-09 |
|
| The novel antidyskinetic drug sarizotan elicits different functional responses at human D2-like dopamine receptors. | 2006-09 |
|
| Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties. | 2006-09 |
|
| Investigation of sarizotan's impact on the pharmacokinetics of probe drugs for major cytochrome P450 isoenzymes: a combined cocktail trial. | 2006-04 |
|
| 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. | 2006-03 |
|
| Effects of sarizotan on the corticostriatal glutamate pathways. | 2005-12-01 |
|
| Contrasting contribution of 5-hydroxytryptamine 1A receptor activation to neurochemical profile of novel antipsychotics: frontocortical dopamine and hippocampal serotonin release in rat brain. | 2005-10 |
|
| Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia. | 2005-09 |
|
| Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats. | 2005-08 |
|
| Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease. | 2005-08 |
|
| Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers. | 2005-07 |
|
| Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study). | 2004-07-15 |
|
| Drugs in development for Parkinson's disease. | 2004-07 |
|
| Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile. | 2004-02 |
|
| 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. | 2003-12 |
|
| Gateways to clinical trials. | 2003-05 |
|
| 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. | 2002-09 |
|
| Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. | 2001-11-27 |
Patents
| Substance Class |
Chemical
Created
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admin
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Edited
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4D56ANR2VD
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