Recent and on-going trials for the treatment of levodopa-induced dyskinesia: a review of the clinical trial databases.

Abstract

L-3,4-dihydroxyphenylalanine (Levodopa)-induced dyskinesia remains a condition for which there are few therapeutic options available. Fortunately, the past 5 years have seen the completion of several clinical trials, some of which yielded positive and encouraging results. Here, we performed a review of the clinical trials that were completed or for which outcomes were disclosed within the past 5 years. Promising results were obtained in Phase II trials with the serotonin type 1A (5-HT_1A) agonist befiradol, the dopamine D₃ receptor antagonist mesdopetam and the phosphodiesterase inhibitor CPL500036. In contrast, the metabotropic glutamate 4 (mGlu₄) receptor negative allosteric modulator foliglurax and JM-010 (a combination of the 5-HT_1A partial agonist buspirone and the and the 5-HT type 1B and 1D [5-HT_1B/1D] agonist zolmitriptan) did not meet their endpoints in Phase II studies. Lastly, robot-assisted Repetitive Transcranial Magnetic Stimulation (rTMS) of the pre-supplementary motor area may be a promising non-pharmacological approach to alleviate dyskinesia.