An assessment of the present and future roles of non-ligand gated ion channel modulators as CNS therapeutics.
Few approved drugs have, as their primary known mechanism of action, modulation of non-ligand gated ion channels. However, these proteins are important regulators of neuronal function through their control of sodium, potassium, calcium and chloride flux, and are ideal candidates as drug discovery targets. Recent progress in the molecular biology and pharmacology of ion channels suggests that many will be associated with specific pharmacological profiles that will include both activators and inhibitors. Ion channels, through their regulation by G-proteins, are a major component of the final common pathway of many drugs acting at classical neuronal receptors. Thus, targeting of the ion channels themselves may confer different profiles of efficacy and specificity to drug action in the brain and spinal cord. Three areas for drug discovery are profiled that the authors consider prime targets for ion channel based therapies, anticonvulsant drugs, cognition enhancing drugs and drugs for improving neurone survival following ischaemia.
Gribkoff
V K
VK
Neuroscience and Genitourinary Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. Gribkofv@BMS.COM
Starrett
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy*; D002491:Central Nervous System Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D008969:Molecular Sequence Data
D002491:Central Nervous System Agents; D007473:Ion Channels