Table 1.
Clinical trials for the treatment of LIDs in PD
| Pharmacological class | Substance (references of completed clinical trials) | Outcome* |
|---|---|---|
| NMDA antagonists | Amantadine27–33 | Effective against LIDs, controversy concerning the duration of antidyskinetic effect |
| ADS-510234 | NCT01397422 (ongoing trial) | |
| Remacemide35 | No antidyskinetic effects | |
| Dextromethorphan37 | Reduced dyskinesia by 30%–40% | |
| AVP-923 | NCT01767129 (ongoing trial) | |
| Memantine40–42 | Possibly effective against LIDs, good tolerability and safety | |
| CP-101,60646 | Mild antidyskinetic effect, no improvement in parkinsonism, side effects | |
| Neu-120 | NCT00607451 (status unknown) | |
| mGluR antagonists | AFQ05658,59 | Reduced established LIDs, no negative effect on parkinsonism, safety and tolerability concerns NCT01173731 (ongoing trial) |
| Dipraglurant (AX48621)61 | Improved parkinsonism and dyskinesia NCT01336088 (completed) | |
| AMPA antagonists | Talampanel | NCT00108667, NCT00036296, NCT00004576 (all trials completed, but no published data available) |
| Perampanel66–68 | No antidyskinetic effects | |
| α2-adrenergic receptor antagonists | Idazoxan72,73 | Controversial results concerning effectiveness and adverse-effects profile |
| Fipamezole74 | Only partially effective NCT01149811, NCT01140841 (completed, no published data available) | |
| Adenosine A2A receptor antagonist | Preladenant (Sch 420814)84,85 | Increase in dyskinesia rates, improvement in parkinsonism |
| Istradefylline86–90 | Improvement in UPDRS, increased dyskinesia rates | |
| Tozadenant (SYN115)91 | No effect in dyskinesia, improvement in parkinsonian symptoms | |
| Nicotinic receptors agonists | Nicotine98,100,101 | Serious adverse effects NCT00957918 (completed, no published data) |
| SIB-1508Y | Very low tolerabilitya | |
| Partial dopamine agonists | Aripiprazole105 | Effective against LIDs, well tolerated |
| Pardoprunox107,108 | Effective against LIDs and improvement in UPDRS motor score | |
| Aplindore | NCT00623324 (completed, no published data available) | |
| Monoamine oxidase-B inhibitors | Selegiline111,115,116 | Controversial results concerning efficacy against LIDs |
| Rasagiline112 | Partially effective against LIDs | |
| Safinamide114 | Improvement of LIDs | |
| 5HT agonists | Tandospirone118 | No antidyskinetic effects, worsening of parkinsonism |
| Sarizotane119,121,122 | Controversial results concerning efficacy against LIDs, probably not effective | |
| Piclozotan | NCT00623363 (completed, no published data available) | |
| Other treatments | Valproate125 | No antidyskinetic effect |
| Gabapentin126 | No antidyskinetic effect | |
| Zonisamide127 | Dose-dependent effectiveness against LIDs | |
| Levetiracetam128–130,133 | Only mild antidyskinetic effect | |
| Topiramate | NCT00296959 (early termination due to slow recruitment) | |
| ACR325 (odopidine) | NCT01023282 (completed, but no published data are available) |
Notes:
a
Study redesigned due to tolerability issues
*
status verified on August 22, 2013.
Abbreviations: LIDs, levodopa-induced dyskinesias; PD, Parkinson’s disease; NMDA, N-methyl-d-aspartate; mGluRs, metabotropic glutamate receptors; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; 5HT, 5-hydroxytryptamine; UPDRS, Unified Parkinson’s Disease Rating Scale.