SEROTONIN, 5-HT2 RECEPTORS, AND THEIR BLOCKADE BY NAFTIDROFURYL - A TARGETED THERAPY OF VASCULAR DISEASES

The importance and the various effects of serotonin (5-HT) in cardiova scular diseases are reviewed, with particular emphasis on the involvem ent of 5-HT2 receptors as mediators of the biological responses of ves sels and blood platelets to 5-HT. The importance of 5-HT in peripheral and cerebral ischemia is shown by the key role it plays in inducing v asoconstriction, platelet aggregation, vascular permeability, and cell proliferation. Of particular importance is the 5-HT-selective hyperse nsitivity developing in vessels/platelets shortly after acute ischemia or early in the development of chronic vascular diseases. The mechani sms of action of naftidrofuryl are described, showing that this drug o ffers a particularly interesting profile of having both metabolic and vascular effects. Naftidrofuryl improves glucose aerobic metabolism by an action on succinodehydrogenase and improves the blood supply and t he ischemic damage of the vessel wall by blocking specifically 5-HT2 r eceptors. The latter property permits an inhibition of the deleterious , multiple effects of 5-HT at sites of vascular injury, without influe ncing the general circulatory bed. Therefore, naftidrofuryl appears to be an anticonstrictor and not, as previously thought, a vasodilator. As a consequence, naftidrofuryl has a targeted impact without vasodila tor-linked side effects such as hypotension or the steal phenomenon.