Low-dose diazepam with NS-398 combination has twice the neuroprotective effect of NS-398 alone

Status epilepticus, prolonged seizures, can lead to significant neurological deficits and, rarely, even death. The anticonvulsant diazepam, a first line therapy for the condition, is neuroprotective when administered in high doses within two hours from seizure onset. Researchers at the 64th AES Annual Meeting now report that the combination of low-dose diazepam and NS-398, a COX-2 inhibitor, has twice the neuroprotective effect of NS-398 alone.

Status epilepticus results in the production of cycloozygenase-2 (COX-2) an inflammatory enzyme associated with neuronal death. Researchers at the University of Utah School of Medicine had previously found that NS-398 alone decreased neuronal damage by about 27 percent. When administered with diazepam, however, the reduction in cell damage increased to more than 60 percent. (Abstract 1.317A)

The study involved 25 laboratory animals with induced status epilepticus and divided into three nearly equal groups - a diazepam only treated group, a diazepam plus NS-398 treated group, and a group injected with the non-drug carrying vehicle only.

According to first author Christina Trandafir, "The combination of low-dose diazepam with NS-398 leads to more effective neuroprotection in the hippocampus than NS-398 alone, and this occurs without an effect on the electrical activity during status epilepticus. Although the combination of drugs did not change the seize activity, neuronal death was greatly decreased. By having such a major protective effect, these drugs might improve the cognitive outcome, such as memory and learning, after status epilepticus. They might also reduce the severity of chronic epilepsy that often develops after status."

Ongoing monitoring of the animals treated with low-dose diazepam and NS-398 will determine the severity of epilepsy (spontaneous seizures) in these animals compared with the control group treated with the non-drug vehicle. Behavioral testing several months after status epilepticus will also be conducted to determine if animals treated with diazepam and the COX-2 inhibitor exhibit better memory and learning capacity than the vehicle-only treated group.


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