Sarizotan (EMD 128130) is an orally active compound that acts as an agonist for serotonin 5-HT 1A receptors and dopamine receptors, with IC50 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-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), 5-HT2B receptor:108 nM (IC50, human), D3 receptor:6.8 nM (IC50, human), 5-HT3 receptor:3500 nM (IC50, NG 108 cells), D2 receptor:15.1 nM (IC50, rat), D2 receptor:17 nM (IC50, human), D4.2:2.4 nM (IC50, human), 5-HT1D receptor:500 nM (IC50, calf), 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)

Sarizotan exhibits concentration-dependent inhibition of electrically-induced contractions, achieving an inhibition concentration (IC50) value of 150 nM, with a maximum efficacy (E max) of 40% observed at a concentration of 1 mM[1].

Sarizotan administered at a dose of 10 mg/kg orally, notably reduces 5-HT levels in the striatum and its metabolite 5-HIAA in the frontal cortex and hippocampus, while substantially enhancing DA metabolites DOPAC and HVA in the same regions[1]. This compounds symbolizes a novel strategy in addressing extrapyramidal motor disorders such as l-DOPA-induced dyskinesia in Parkinson's disease[1]. Furthermore, in a study involving male Sprague-Dawley rats (weighing 220-240 g and showing a strong rotational response), local administration of Sarizotan at doses of 10 ng and 1 μg effectively mitigated levodopa-induced dyskinesias in 6-OHDA-lesioned rats[2]. These rats received the compound via an injection cannula placed through the STN (V -8.4 mm from skull), utilizing a microinfusion pump over a period of 22 days. Notably, on the 23rd day, a significant reduction in total dyskinesia scores was observed in levodopa-treated rats at the higher doses of Sarizotan (10 ng and 1 μg) compared to those treated with levodopa alone (p<0.05, p<0.01, respectively).