Sarizotan (EMD 128130) is an orally active compound that acts as an agonist for serotonin 5-HT 1A receptors and dopamine receptors. It has shown potent activity with IC 50 values of 6.5 nM for rat 5-HT 1A , 0.1 nM for human 5-HT 1A , 15.1 nM for rat D 2 , 17 nM for human D 2 , 6.8 nM for human D 3 , and 2.4 nM for human D 4.2 .

5-HT2A receptor:587 nM (IC50, human, antagonist site), 5-HT2A receptor:960 nM (IC50, rat, agonist site), 5-HT2C receptor:800 nM (IC50, pig), 5-HT6 receptor:3300 nM (IC50, human), 5-HT7 receptor:10 nM (IC50, human), 5-HT3 receptor:3500 nM (IC50, NG 108 cells), D3 receptor:6.8 nM (IC50, human), 5-HT2B receptor:108 nM (IC50, human), 5-HT1A receptor:0.1 nM (IC50, human), 5-HT1A receptor:6.5 nM (IC50, rat), 5-HT1B receptor:600 nM (IC50, rat), 5-HT5A receptor:313 nM (IC50, human), D 4.2:2.4 nM (IC50, human), D2 receptor:15.1 nM (IC50, rat), D2 receptor:17 nM (IC50, human), 5-HT1D receptor:500 nM (IC50, calf)

Sarizotan concentration-dependently inhibits the electrically-induced contractions with an IC 50 value of 150 nM (E max 40% at 1 mM)[1].

Sarizotan (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[1]. Sarizotan represents a new approach for the treatment of extrapyramidal motor complications such as l-DOPA-induced dyskinesia in Parkinson’s disease[1]. Sarizotan (10 ng and 1 μg, local administration) attenuates levodopa-induced dyskinesias in 6-OHDA-lesioned rats[2]. Animal Model: Male Sprague-Dawley rats weighing 220-240 g (exhibiting a vigorous rotational response)[2]. 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).