Authors: Lane Brown, R.; Strassmaier, Timothy; Brady, James D.; Karpen, Jeffrey W.

Source: Current Pharmaceutical Design, Volume 12, Number 28, October 2006 , pp. 3597-3613(17)

Publisher: Bentham Science Publishers

Abstract:

Cyclic nucleotide-gated (CNG) ion channels play a central role in vision and olfaction, generating the electrical responses to light in photoreceptors and to odorants in olfactory receptors. These channels have been detected in many other tissues where their functions are largely unclear. The use of gene knockouts and other methods have yielded some information, but there is a pressing need for potent and specific pharmacological agents directed at CNG channels. To date there has been very little systematic effort in this direction - most of what can be termed CNG channel pharmacology arose from testing reagents known to target protein kinases or other ion channels, or by accident when researchers were investigating other intracellular pathways that may regulate the activity of CNG channels. Predictably, these studies have not produced selective agents. However, taking advantage of emerging structural information and the increasing knowledge of the biophysical properties of these channels, some promising compounds and strategies have begun to emerge. In this review we discuss progress on two fronts, cyclic nucleotide analogs as both activators and competitive inhibitors, and inhibitors that target the pore or gating machinery of the channel. We also discuss the potential of these compounds for treating certain forms of retinal degeneration.

Keywords: cGMP; Polymer-linked ligand dimers (PLDs); Dichlorobenzamil (DCB); CNGA1 Channels; HCN channels

Document Type: Research article

Affiliations: 1: Department of Physiology and Pharmacology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., L334, Portland OR 97239.

Publication date: 2006-10-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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