Table 3.
Some of the therapeutic trials on transgenic SOD1-G93A mice with compounds involved in glutamate-mediated excitotoxicity
| Agent (mechanism of action with respect to glutamate homeostasis) | Dose | Route | Start of therapy (days) | Onset change (%) | Survival change | Reference |
|---|---|---|---|---|---|---|
| Carboxyfullerene (block excitotoxicity mediated NMDA and AMPA receptors) | 15 mg/kg/day | i.p. | 73 | Increase | Increase | 40 |
| Ceftriaxone (increase expression levels and activity of EAAT2) | 200 mg/kg/day | i.p. | 42 | Increase | +11% | 118 |
| Gabapentin (decrease of glutamate release) | 3% diet | diet | 50 | − | +5% | 59 |
| GPI-1046 (increase expression levels and activity of EAAT2) | 50 mg/kg twice a day | p.o. | 150 - SOD1-G93A low expressors | − | +12% | 52 |
| Memantine (noncompetitive NMDA antagonist) | 10 mg/kg twice a day | s.c. | 70 | − | +7% | 150 |
| NBQX (AMPA receptor antagonist) | 8 mg/kg 5 times a week | i.p. | 70 | Increase | +10 | 143 |
| Riluzole (decrease of glutamate release, increase of glutamate uptake) | 50 mg/kg/day | p.o. | 50 | − | +10% | 59 |
| Topiramate (decrease of glutamate release, block of AMPA receptors) | 50 mg/kg | p.o | 30 | − | − | 91 |
| NDGA (increase of glutamate transport) | 1 mg/day | s.c. | 90 | − | − | 16 |
| MPEP (block of mGluR5) | 30 mg/kg/day | i.p. | 40 | Increase | Increase | 114 |
| ZK 187638 (noncompetitive antagonist of AMPA receptor) | 140 mg/kg once in 2 days | p.o. | 77 | Increase | Increase | 134 |
i.p., intraperitoneal; p.o., per osmosis; s.c., subcutaneous; NBQX, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzoquinoxaline-2,3-dione; MPEP, 2-methyl-6-(phenylethylnyl)pyridine; NDGA, nordihydroguaiaretic acid.