Voltage-gated Na+ channels as targets for anticonvulsant, analgesic and neuroprotective drugs

Voltage-dependent Na+ channels have been recognized for many years as targets for local anesthetic and antiarrhythmic drugs. In the past ten years, Na+ channels have increasingly been recognized as a target for anticonvulsant drugs (e.g. phenytoin, carbamazepine, lamotrigine). This same class of drugs has been used to treat neuropathic pain such as from trigeminal neuralgia, diabetic neuropathy or other nerve damage. More recently, it has become clear from results in vitro and with animal models that Na+ channel modulators similar to anticonvulsants have neuroprotective actions against ischemia, trauma and neurodegenerative diseases. This brief review covers recent advances in the molecular biology of mammalian Na+ channels and the evidence that Na+ channel blockade with both conventional drugs and recently synthesized compounds may be useful for treatment of a variety of CNS diseases.