Abstract
Nitric oxide (NO) releasing drugs have helped patients suffering from angina pectoris for more than a century. In the 1970s NO-sensitive guanylyl cyclase was identified as the target of NO. Since then, three different isoforms of the enzyme have been identified. All NO-releasing drugs act by binding of NO to the prosthetic heme group common to all three isoforms. They thus act all as isoform-unspecific substances. This review addresses recently developed drugs that activate NO-sensitive guanylyl cyclase independent of NOrelease. They have great potential in the treatment of angina pectoris, hypertension and erectile dysfunction. The molecular target has been validated by the successful clinical use of NO-releasing drugs for more than a century. At the same time the mode of action of these drugs is entirely new. The development of highly isoform-specific derivatives with distinct pharmacological profiles is now an open possibility with great potential.
Keywords: nitric oxide, guanylyl cyclase, glyceryl trinitrste, bay41-2272, bay41-8543, bay58-2667
Current Medicinal Chemistry
Title: Drugs that Activate Specific Nitric Oxide Sensitive Guanylyl Cyclase Isoforms Independent of Nitric Oxide Release
Volume: 10 Issue: 4
Author(s): Sonke Behrends
Affiliation:
Keywords: nitric oxide, guanylyl cyclase, glyceryl trinitrste, bay41-2272, bay41-8543, bay58-2667
Abstract: Nitric oxide (NO) releasing drugs have helped patients suffering from angina pectoris for more than a century. In the 1970s NO-sensitive guanylyl cyclase was identified as the target of NO. Since then, three different isoforms of the enzyme have been identified. All NO-releasing drugs act by binding of NO to the prosthetic heme group common to all three isoforms. They thus act all as isoform-unspecific substances. This review addresses recently developed drugs that activate NO-sensitive guanylyl cyclase independent of NOrelease. They have great potential in the treatment of angina pectoris, hypertension and erectile dysfunction. The molecular target has been validated by the successful clinical use of NO-releasing drugs for more than a century. At the same time the mode of action of these drugs is entirely new. The development of highly isoform-specific derivatives with distinct pharmacological profiles is now an open possibility with great potential.
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Cite this article as:
Behrends Sonke, Drugs that Activate Specific Nitric Oxide Sensitive Guanylyl Cyclase Isoforms Independent of Nitric Oxide Release, Current Medicinal Chemistry 2003; 10 (4) . https://dx.doi.org/10.2174/0929867033368286
DOI https://dx.doi.org/10.2174/0929867033368286 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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