Because ischemic neuronal death is triggered by several parallel mechanisms, a combination of drugs active against individual death-promoting mechanisms may have synergistic effects.
Dexanabinol is a noncompetitive
NMDA antagonist with anti-inflammatory effects and
tempol is a
nitroxide antioxidant. Therefore, we explored whether their combined use results in smaller
infarct volumes as compared with their individual administration. Rats underwent permanent
middle cerebral artery occlusion (PMCAO) and were given vehicle,
dexanabinol alone,
tempol alone, or a combination of
dexanabinol and
tempol (n = 13 per group) 1 h later. Five animals in each group were evaluated with a motor rating scale 24 h after PMCAO and the
infarct volumes were then measured. The remaining animals were examined with motor and behavioral scales up to 30 days after PMCAO and their
infarct volumes were then determined. Motor disability and water maze latencies at all time points examined and
infarct volumes at days 1 and 30 were significantly reduced in all active treatment groups when compared with vehicle. However, no significant differences were observed between the active treatment groups. In conclusions, combination
therapy with
dexanabinol and
tempol does not appear to have additional
neuroprotective effects compared to those conferred by each agent alone even when administered at optimal timing and dosing. Therefore, a ceiling
neuroprotective effect that is impossible to overcome may exist.