NO-aspirin: mechanism of action and gastrointestinal safety.
Nitric oxide-releasing aspirins are new chemical entities obtained by adding a nitric oxide-releasing moiety to aspirin. NCX-4016 is the prototype of this family of molecules. NCX-4016 consists of the parent molecule (aspirin) linked to a 'spacer' via an ester linkage, which is in turn connected to a nitric oxide-releasing moiety. Both aspirin and nitric oxide moieties of NCX-4016 contribute to its effectiveness, the latter occurring via both cyclic guanosyl monophosphate-dependent and -independent mechanisms. In vitro studies have shown that NCX-4016 inhibits platelet aggregation induced by aspirin-sensitive (arachidonic acid) and aspirin-insensitive (thrombin) agonist. In contrast to aspirin, NCX-4016 exerts a multilevel regulation of inflammatory target, including caspase-1 and NF-kappaB. This broad spectrum of activities translates to an increased potency of this drug in modulating cardiovascular inflammation. Human studies have shown, that while nitric oxide-aspirin maintains its anti-thrombotic activity, it spares the gastrointestinal tract. Indeed, a 7-day course of NCX-4016 results in 90% reduction of gastric damage caused by equimolar doses of aspirin. Further studies are ongoing to define whether this superior anti-inflammatory and anti-thrombotic profile translates in clinical benefits in patients with cardiovascular diseases.
Fiorucci
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S
Gastrointestinal and Liver Unit, Department of Internal Medicine, University of Perugia, Perugia, Italy. fiorucci@unipg.it
Del Soldato
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P
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D004064:Digestive System / Q000098:blood supply / Q000187:drug effects*; D006801:Humans; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D012039:Regional Blood Flow
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009569:Nitric Oxide; C102148:nitroaspirin; D001241:Aspirin