COX-inhibiting nitric oxide donators (CINODs), also known as NO-NSAIDs, are a new class of

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

(NSAID) developed with the intention of providing greater safety than existing NSAIDs. These compounds were first described by John Wallace and colleagues. CINODs are compounds generated by the fusion of an existing NSAID with a

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

(NO)-donating

moiety Moiety may refer to: Chemistry * Moiety (chemistry), a part or functional group of a molecule ** Moiety conservation, conservation of a subgroup in a chemical species Anthropology * Moiety (kinship), either of two groups into which a society is ...

by chemical means, usually by

ester linkage In chemistry, an ester is a chemical compound, compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an Alcohol ...

. CINODs retain the anti-inflammatory efficacy of NSAIDs via inhibition of cyclooxygenase (COX) while arguably improving upon gastric and vascular safety, most likely via

vasorelaxation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...

, inhibition of

leukocyte White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

adhesion and inhibition of

caspases Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cystei ...

, all known effects of NO. The first CINODs were developed in the 1990s, and as yet none have been approved for use by the general public. The importance of developing such drugs was increased when COX-2-specific NSAIDs rofecoxib (Vioxx) and

lumiracoxib Lumiracoxib is a COX-2 selective inhibitor nonsteroidal anti-inflammatory drug. Its structure is different from that of other COX-2 inhibitors, such as celecoxib: lumiracoxib is an analogue of diclofenac (one chlorine substituted by fluorine, ...

(Prexige) were removed from major pharmaceutical markets in the mid-2000s due to vascular safety concerns. In addition, traditional NSAIDs increase

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

and interfere with the actions of

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests tha ...

drugs. Several CINODs are currently being tested in

clinical trials Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

, the most advanced of which are being conducted by the

French French (french: français(e), link=no) may refer to: * Something of, from, or related to France ** French language, which originated in France, and its various dialects and accents ** French people, a nation and ethnic group identified with Franc ...

pharmaceutical company NicOx, whose flagship compound

naproxcinod Naproxcinod (nitronaproxen) is a nonsteroidal anti-inflammatory drug (NSAID) developed by the French pharmaceutical company NicOx. It is a derivative of naproxen with a nitroxybutyl ester to allow it to also act as a nitric oxide (NO) donor. Thi ...

(NO-naproxen, nitronaproxen) is in phase III trials for the treatment of osteoarthritis. Naproxcinod is a fusion of naproxen and a NO-donating group. Other CINODs are also being tested by NicOx for the treatment of diseases in which inflammation plays a role.

References

Nonsteroidal anti-inflammatory drugs {{analgesic-stub