The combination of numerous classic drugs with
nitric oxide donors has led to the development of new compounds with promising therapeutic activities in a great variety of situations, including cardiovascular and respiratory systems, ocular pressure,
inflammation, and
pain. One of the first compounds developed was
NCX-701 or
nitroparacetamol, resulting from the combination of
paracetamol, a classic and popular
analgesic used in a great number of over-the-counter medications because of its
antipyretic and
analgesic properties, and a nitrooxybutyroyl moiety, which releases
nitric oxide at a low but steady level. Although
paracetamol is devoid of most of the gastrointestinal toxicity associated with
aspirin-like drugs, this type of compounds was first designed to take advantage of the cytoprotective properties of
nitric oxide when released at low concentrations. However, the combination of these molecules also resulted in an unexpected enhancement of the
analgesic activity of
paracetamol. In fact,
NCX-701 has been shown to be effective in acute nociception as well as in
neuropathic pain, situations in which
paracetamol and other COX inhibitors are devoid of any effect. In addition,
NCX-701 is more potent and, in some circumstances, more effective than its parent compound in different models of inflammatory
pain. Furthermore, whereas
paracetamol lacks any effective antiinflammatory action,
NCX-701 might reduce
inflammation. All these results taken together imply that the mechanism of action of
NCX-701 is different from that of
paracetamol, although it is not yet established for either molecule.
NCX-701 appears to be a promising compound in the treatment of different types of
pain, with a likely better profile of side effects than its parent molecule,
paracetamol. Although recent clinical trials provided data consistent with the preclinical profile of
NCX-701, further studies are needed to support its clinical use.