Sarizotan (Merck KgaA) is a novel compound belonging to the aminomethyl chro-mane chemical group, which was initially developed as an atypical antipsychotic, but is now being evaluated to treat dopaminergic-induced dyskinesia in PD. The drug has affinity for 5-HT1A, D2, D3, and D4 receptors. After oral ingestion, it is rapidly absorbed and highly protein bound, but readily crosses the blood-brain barrier. The terminal serum T1/2 is approximately seven hours, and the drug is extensively metabolized by N-dealkylation and hydroxylation (53).
In animal models of PD, including MPTP primates, sarizotan improved drug-induced dyskinesia without worsening motor function (54). In an open-label trial of
64 dyskinetic PD subjects, sarizotan, at doses ranging from 2 mg BID to 10 mg BID, prolonged the amount of on time without dyskinesia (55). PD symptoms were not worsened, as assessed by amount of off time or UPDRS scores, although some patients did report worsening of parkinsonism as an adverse event. Additional adverse events reported included sedation and nausea. Higher doses have been associated with suppression of the cortisol response to ACTH challenge, but this was not seen in PD. A large multicenter Phase III trial did not demonstrate a difference between sarizotan and placebo and consequently the development of this compound for PD has been abandoned (56).
Was this article helpful?