Nitric oxide is formed in the endothelial cells inside blood vessels. Cardiovascular diseases attack these cells, reducing the amount of nitric oxide that is produced, which, in turn, contributes to further progression of these diseases.
Drugs already exist that can provide additional NO in the cardiovascular system. However, these affect the whole body - not just the diseased tissue - creating unwanted side effects. PharmaLinks claims its compounds can target endothelial dysfunction in diseased tissues without affecting normal tissue in other organs.
The compounds are synthetic pteridines, which imitate the natural enzyme cofactor, tetrahydrobiopterin, which is involved in the synthesis of nitric oxide. Although treatment with tetrahydrobiopterin can increase nitric oxide levels in the body, it has a very short half life, and has to be injected directly into arteries because it permeates cells poorly.
Evidence from animal trials indicates that the synthetic pteridines restore nitric oxide formation in diseased areas more effectively than tetrahydrobiopterin. They are also more stable and can be orally administered.
To date the compounds have been tested preclinically in cardiovascular disease and pulmonary hypertension, and now PharmaLinks plans to extend research to animal models of diabetes and atherosclerosis.
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