NEUROPROTECTION - RATIONALE FOR PHARMACOLOGICAL MODULATION OF NA-CHANNELS()

The primary factor detrimental to neurons in neurological disorders as sociated with deficient oxygen supply or mitochondrial dysfunction is insufficient ATP production relative to their requirement. As a large part of the energy consumed by brain cells is used for maintenance of the Na+ gradient across the cellular membrane, reduction of energy dem and by downmodulation of voltage-gated Na+-channels is a rational stra tegy for neuroprotection. In addition, preservation of the inward Nagradient may be beneficial because it is an essential driving force fo r vital ion exchanges and transport mechanisms such as Ca2+ homeostasi s and neurotransmitter uptake.