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 cardiovascular diseases are reviewed, with particular emphasis on the involvement of 5-HT2 receptors as mediators of the biological responses of vessels 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 vasoconstriction, platelet aggregation, vascular permeability, and cell proliferation. Of particular importance is the 5-HT-selective hypersensitivity developing in vessels/platelets shortly after acute ischemia or early in the development of chronic vascular diseases. The mechanisms of action of naftidrofuryl are described, showing that this drug offers 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 the ischemic damage of the vessel wall by blocking specifically 5-HT2 receptors. The latter property permits an inhibition of the deleterious, multiple effects of 5-HT at sites of vascular injury, without influencing 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 vasodilator-linked side effects such as hypotension or the steal phenomenon.
Wiernsperger
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NF
International Pharmacological Development, Lipha Labs, Lyon, France.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009257:Nafronyl / Q000494:pharmacology* / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D014652:Vascular Diseases / Q000188:drug therapy*; D014661:Vasoconstriction / Q000187:drug effects
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D009257:Nafronyl