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. 2007 Aug 9;13(3):279–295. doi: 10.1111/j.1527-3458.2007.00016.x

Nitroparacetamol (NCX‐701) and Pain: First in a Series of Novel Analgesics

E Alfonso Romero‐Sandoval 2, M Mar Curros‐Criado 1, Gema Gaitan 3, Carlos Molina 1, Juan F Herrero 1
PMCID: PMC6494127  PMID: 17894645

ABSTRACT

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.

Keywords: COX inhibitors, Cyclooxygenase, Inflammation, Neuropathy, Nitric oxide, Nitroparacetamol, Nociception, NCX‐701, NSAIDs, Pain, Paracetamol

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Aknowledgments

Most of the work performed by the authors and presented here has been supported by grants from the Spanish Ministry for Science and Technology (grant SAF2005‐06242‐C03‐03) and Comunidad de Madrid/Universidad de Alcala (grant CAM‐UAH2005/003). M. Mar Curros‐Criado is a fellow of the University of Alcala. We also thank Mr. Lawrence Baron for the English and scientific revision of the manuscript.

Conflict of Interest: The authors' research with NCX‐701 has been partially funded by the manufacturer of the drug (NiCox S.A.)

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