Abstract
This overview depicts the voltage-regulated potassium channel, which is
found in the CNS, and the emerging therapeutic applications of potassium channel
modulators. It also discusses the recent developments in our understanding of the
mechanisms, that control the activity of a series of channels, that are selective for
potassium ions. It has been long recognized that the excitability of cells is mediated by
proteins, which can modulate the ability of potassium ions to travel across the cell
membrane. Going back ten years, it has become increasingly clear that, potassium ion
channels represent an excellent target for novel drug design. Investigating the role of
potassium channels in treating human diseases continues to be a growing field of
research. The ability of potassium channels to regulate membrane potential accords a
central role in varied cellular processes that govern excitability, action potential
characteristics, stimulus secretion coupling, cell volume regulation, and epithelial
electrolyte transport. Attention from medicinal chemists to potassium channels as drug
targets has grown with the realization that a variety of potassium channel openers offer
significant therapeutic opportunities in cardiac, smooth muscle, neuronal, immune, and
secretary systems. Progressive improvements in molecular biology have enabled
regular cloning of potassium channels of interest, and defined families of these
channels have facilitated a comprehensive understanding of their function. Importantly
many families of increasingly selective small molecules have emerged as target
validation and clinical proof of principle. Many reviews have appeared summarizing
the synthesis and therapeutic potential of these channels. The scope of this report is to
make you aware of potassium channel biology, which leads to a more expedient identification of agents for the treatment of CNS disorders, emphasizing developments in
medicinal chemistry based on potassium channels where modulators would have
considerable clinical potential. While every effort has been made to include all relevant
reports in this discussion, any omission is inadvertent and we apologize for the same.