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
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
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 |
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Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. | 2001 Nov 27 |
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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 |
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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 |
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Gateways to clinical trials. | 2003 May |
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Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile. | 2004 Feb |
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Drugs in development for Parkinson's disease. | 2004 Jul |
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Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study). | 2004 Mar-Apr |
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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 |
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Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease. | 2005 Aug |
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Effects of sarizotan on the corticostriatal glutamate pathways. | 2005 Dec 1 |
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Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers. | 2005 Jul |
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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 |
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Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia. | 2005 Sep |
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Investigation of sarizotan's impact on the pharmacokinetics of probe drugs for major cytochrome P450 isoenzymes: a combined cocktail trial. | 2006 Apr |
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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 |
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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 |
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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 |
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In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles. | 2006 Sep |
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The novel antidyskinetic drug sarizotan elicits different functional responses at human D2-like dopamine receptors. | 2006 Sep |
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Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties. | 2006 Sep |
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Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial. | 2007 Jan 15 |
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[Dyskinesia in Parkinson's disease--major clinical features, aetiology, therapy]. | 2007 Jul |
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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 |
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Differential agonist and inverse agonist profile of antipsychotics at D2L receptors coupled to GIRK potassium channels. | 2007 Mar |
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Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects. | 2007 May |
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Current approaches to the treatment of Parkinson's disease. | 2008 Aug |
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Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells. | 2008 Feb 26 |
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Effects of antipsychotics and reference monoaminergic ligands on marble burying behavior in mice. | 2008 Mar |
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Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys. | 2009 Jul |
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Local administration of sarizotan into the subthalamic nucleus attenuates levodopa-induced dyskinesias in 6-OHDA-lesioned rats. | 2009 Jun |
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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 |
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Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity. | 2010 Nov 16 |
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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
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00105508
Subjects will receive sarizotan 1 milligram orally twice daily for 24 weeks.
Route of Administration:
Oral
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FDA ORPHAN DRUG |
484015
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NCI_THESAURUS |
C1509
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CHEMBL220808
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7748
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C77567
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C443959
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DB06454
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Sarizotan
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6918388
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m9782
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DTXSID80956632
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SUB04329MIG
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ACTIVE MOIETY
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