Discovery of active substances could revolutionise cardiovascular therapy
Active substances that could have clear benefits over conventional organic nitrates in the treatment of cardiovascular diseases have been discovered by Bayer scientists. Some of these novel substances, known as soluble guanylyl cyclase activators, are already undergoing Phase I clinical development.1
Studies have shown that these new substances, such as BAY 58-2667, exert a strong vasodilative effect, but in contrast to nitrates also inhibit blood platelet aggregation and thus exert antithrombotic effects. In clinical tests, the substances demonstrated pronounced cardiovascular effects without producing headache.
For almost 150 years, nitrates have been a mainstay of drug treatment for cardiovascular diseases such as angina pectoris. Nitrates act by activating soluble guanylyl cyclase (sGC) through bioconversion to form nitric oxide (NO). NO dilates the blood vessels and thus improves the cardiac blood supply. Soluble guanylyl cyclase induces cellular binding of NO and facilitates the formation of the messenger substance cGMP (cyclic guanosine monophosphate), which regulates a number of important cell functions.
The substances from Bayer's research programme activate soluble guanylyl cyclase independently of NO. Their pharmacological properties mean that they could be used to treat hypertension, heart failure, coronary heart disease, arteriosclerosis and thrombosis.