Sarizotan

Sarizotan (EMD 128130) is an orally active serotonin 5-HT1A receptor and dopamine receptor agonist. Sarizotan (EMD 128130) exhibits IC50 values of 6.5 nM (rat 5-HT1A), 0.1 nM (human 5-HT1A), 15.1 nM (rat D2), 17 nM (human D2), 6.8 nM (human D3) and 2.4 nM (human D4.2), respectively[1].

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

5-HT1A Receptor:6.5 nM (IC50, rat)

5-HT1A Receptor:0.1 nM (IC50, human)

D2 Receptor:15.1 nM (IC50, rat)

D2 Receptor:17 nM (IC50, human)

D3 Receptor:6.8 nM (IC50, human)

D4.2:2.4 nM (IC50, human)

5-HT1B Receptor:600 nM (IC50, rat)

5-HT1D Receptor:500 nM (IC50, calf)

5-HT2A Receptor:960 nM (IC50, rat, agonist site)

5-HT2A Receptor:587 nM (IC50, human, antagonist site)

5-HT2B Receptor:108 nM (IC50, human)

5-HT2C Receptor:800 nM (IC50, pig)

5-HT3 Receptor:3500 nM (IC50, NG 108 cells)

5-HT5A Receptor:313 nM (IC50, human)

5-HT6 Receptor:3300 nM (IC50, human)

5-HT7 Receptor:10 nM (IC50, human)

Sarizotan concentration-dependently inhibits the electrically-induced contractions with an IC50 value of 150 nM (Emax 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).

[1]. G D Bartoszyk, et al. Sarizotan, a Serotonin 5-HT1A Receptor Agonist and Dopamine Receptor Ligand. J Neural Transm (Vienna). 2004 Feb;111(2):113-26.

[2]. C Marin, et al. Local Administration of Sarizotan Into the Subthalamic Nucleus Attenuates Levodopa-Induced Dyskinesias in 6-OHDA-lesioned Rats. Psychopharmacology (Berl). 2009 Jun;204(2):241-50.