A new dual action neuroprotective agent could provide the basis of potential treatments for stroke and other neurodegenerative disorders (Proceedings of the National Academy of Sciences USA 1999;96:10,824).
The compound, BN 80933, inhibits neuronal nitric oxide synthase and also has antioxidant properties. Both nitric oxide (NO) and reactive oxygen species (ROS) have been implicated in neuronal cell death, say Dr Pierre-Etienne Chabrier (Institut Henri Beaufour, France) and colleagues. They believe that NO and ROS act independently and co-operatively to cause the neuronal damage seen in stroke and trauma. By inhibiting both NO synthase and ROS, the new drug potentially provides a better neuroprotective effect than inhibition of either species alone, they say.
Using animal models, the researchers found that intravenous administration of BN 80933 significantly reduced brain damage induced by trauma or ischaemia. In addition, they report, it still provided significant neuroprotection when administered up to eight hours after injury.
BN 80933 was formed by coupling an antioxidant (a Trolox derivative) via a piperidine chain to an NOS inhibitor (thiopheneamidine). The researchers conclude that BN 80933 "may offer an alternative for the treatment of stroke and perhaps other neurological disorders in humans".