The paper reviews the main approaches used for development of effective therapeutic means directly regulating signaling system "nitric oxide (NO) - soluble guanylate cyclase - cyclic guanosine monophosphate (cGMP)". Special attention is paid to the role of this system in the mechanism of action of so called "old drugs". Using new approaches for investigating the antihypertensive and antiaggregatory action of NO and the role of guanylate cyclase in these processes the priority and fundamental data concerning the elaboration of the molecular basis of directed search and creation of new, effective antihypertensive and antiaggregatory compounds have been obtained. Studies of direct activation of soluble guanylate cyclase by the original NO-donors new activators of this enzyme resulted in discovery of new drugs participating in regulation of haemostasis and vascular tone. The priority data on new inhibitors of NO-dependent activation of guanylate cyclase (among which turn to the drugs) and the possible molecular mechanism of their pharmacological action are presented. It was shown at first time that the signaling system "NO-soluble guanylate cyclase-cGMP" may be involved in the mechanism of the therapeutic action of a number of widely used drugs including those acting as chemotherapeutics and antiprotozoics.
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