Sarizotan (C09-1170-415)

Sarizotan (EMD 128130) is an orally active serotonin 5-HT 1A receptor and dopamine receptor agonist. Sarizotan (EMD 128130) exhibits IC 50 values of 6.5 nM (rat 5-HT 1A ), 0.1 nM (human 5-HT 1A ), 15.1 nM (rat D 2 ), 17 nM (human D 2 ), 6.8 nM (human D 3 ) and 2.4 nM (human D 4.2 ), respectivelyIn VitroSarizotan concentration-dependently inhibits the electrically-induced contractions with an IC 50 value of 150 nM (E max 40% at 1 mM). MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoSarizotan (3, 10 mg/kg, po) at the higher dose slightly decreases 5-HT in the striatum and its metabolite 5-HIAA in frontal cortex and hippocampus. Sarizotan (10 mg/kg, po) substantially increases the DA metabolites DOPAC and HVA in the striatum and frontal cortex . Sarizotan represents a new approach for the treatment of extrapyramidal motor complications such as l-DOPA-induced dyskinesia in Parkinson’s disease . Sarizotan (10 ng and 1 μg, local administration) attenuates levodopa-induced dyskinesias in 6-OHDA-lesioned rats. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Sprague-Dawley rats weighing 220-240 g (exhibiting a vigorous rotational response). Dosage: 1 ng, 10 ng and 1 μg in 0.3 μL solution. Administration: Administered via an injection cannula inserted to the guide cannula through the STN (V -8.4 mm from skull) with the injection cannula connected to a 10-μL syringe and mounted on a microinfusion pump for 22 consecutive days. Result: On day 23, the subthalamic administration of Sarizotan at the higher doses tested (10 ng and 1 μg) significantly decreased the total dyskinesia score in levodopa-treated rats in comparison with the rats treated only with levodopa (p<0.05, p<0.01, respectively).Form:Viscous liquidIC50& Target:5-HT 1A Receptor 6.5 nM (IC 50 , rat) 5-HT 1A Receptor 0.1 nM (IC 50 , human) rD 2 Receptor 15.1 nM (IC 50 , rat) D 3 Receptor 6.8 nM (IC 50 , human) 5-HT 1B Receptor 600 nM (IC 50 , rat) 5-HT 1D Receptor 500 nM (IC 50 , calf) 5-HT 2A Receptor 960 nM (IC 50 , rat, agonist site) 5-HT 2A Receptor 587 nM (IC 50 , human, antagonist site) 5-HT 2B Receptor 108 nM (IC 50 , human) 5-HT 2C Receptor 800 nM (IC 50 , pig) 5-HT 3 Receptor 3500 nM (IC 50 , NG 108 cells) 5-HT 5A Receptor 313 nM (IC 50 , human) 5-HT 6 Receptor 3300 nM (IC 50 , human) 5-HT 7 Receptor 10 nM (IC 50 , human) hD 4.2 Receptor 2.4 nM (IC 50 ) hD 2 Receptor 17 nM (IC 50 ). Specification: 0.98 Molecular Formula: C22H21FN2O Molecular Weight: 348.41 PubChem CID: 6918388 Isomeric SMILES: C1CC2=CC=CC=C2O[C@H]1CNCC3=CC(=CN=C3)C4=CC=C(C=C4)F