Drugs that Activate Specific Nitric Oxide Sensitive Guanylyl Cyclase Isoforms Independent of Nitric Oxide Release

Author: Behrends S.

Source: Current Medicinal Chemistry, Volume 10, Number 4, February 2003 , pp. 291-301(11)

Publisher: Bentham Science Publishers

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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

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/0929867033368286

Publication date: 2003-02-01

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Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.