Table 3.
Pre-clinical and clinical studies with purinergic receptor antagonists in PD
| Compounds | Mechanism of effect | Models | Published | Results |
|---|---|---|---|---|
| KW-6002 (istradefylline) | A2A receptor antagonism | PD patients | 2003 | Improved PD motor scores when added to low-dose l-DOPA |
| KW-6002 (istradefylline) | A2A receptor antagonism | LPS treated rats | 2013 | Enhanced therapeutic effect of l-DOPA |
| Caffeine | A2A receptor antagonism | LPS treated rats | 2013 | Reduced motor impairment |
| Preladenant | A2A receptor antagonism | MPTP treated mice | 2014 | Enhanced therapeutic effect of low doses of l-DOPA |
| 8-Ethoxy-9-ethyladenine | A2A receptor antagonism | 6-OHDA lesioned rats | 2015 | Enhanced effect of low doses of l-DOPA without increased dyskinesia |
| SCH 58261 | A2A receptor antagonism | A2A receptor knockout mice, SH-SY5Y cells | 2015 | Decreased α-synuclein aggregation, prevented neuronal death |
| ZM 241385 | A2A receptor antagonism | A2A receptor knockout mice, SH-SY5Y cells | 2015 | Decreased α-synuclein aggregation, prevented neuronal death |
| Preladenant | A2A receptor antagonism | PD patients | 2017 | Failed (was not superior to placebo) in phase III clinical trial |
| Vipadenant | A2A receptor antagonism | PD patients | 2009 | Failed (was not superior to placebo) |
| Tozadenant | A2A receptor antagonism | PD patients | 2017 | Failed in phase III clinical trial (induced agranulocytosis) |
| NF449 | P2X1 receptor antagonism | H4 cells | 2015 | Prevented α-synuclein aggregation |
| A-438079 | P2X7 receptor antagonism | 6-OHDA lesioned rats | 2010 | Prevented depletion of DA in striatum |
| BBG | P2X7 receptor antagonism | 6-OHDA lesioned rats | 2014 | Reverted dopaminergic neurons loss in substantia nigra |
| BBG | P2X7 receptor antagonism | BV2 microglia cells | 2015 | Decreased ROS production induced by α-synuclein |
| PPADS | P2X7 receptor antagonism | SH-SY5Y cells | 2017 | Prevented abnormal calcium influx induced by α-synuclein |
| AZ 11645373 | P2X7 receptor antagonism | SH-SY5Y cells | 2017 | Prevented abnormal calcium influx induced by α-synuclein |
| AP4A | P2Y2/P2Y4 antagonism | 6-OHDA lesioned rats | 2003 | Reduced dopaminergic neurons loss |
| MRS2578 | P2Y6 receptor antagonism | SH-SY5Y cells | 2017 | Delayed neuronal loss |