COX-inhibiting nitric oxide donators (CINODs), also known as NO-NSAIDs, are a new class of
nonsteroidal anti-inflammatory drug (NSAID) developed with the intention of providing greater safety than existing NSAIDs.[1][2][3][4]
These compounds were first described by John Wallace[5] and colleagues. CINODs are
compounds generated by the fusion of an existing NSAID with a
nitric oxide (NO)-donating
moiety by chemical means, usually by
ester linkage. 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, inhibition of
leukocyteadhesion and inhibition of
caspases, 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 NSAIDsrofecoxib (Vioxx) and
lumiracoxib (Prexige) were removed from major pharmaceutical markets in the mid-2000s due to
vascular safety concerns. In addition, traditional NSAIDs increase
blood pressure and interfere with the actions of
antihypertensive drugs. Several CINODs are currently being tested in
clinical trials, the most advanced of which are being conducted by the
Frenchpharmaceutical companyNicOx, whose flagship compound
naproxcinod (NO-naproxen, nitronaproxen) is in
phase III trials for the treatment of
osteoarthritis.[6] 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.[7]
References
^Wallace JL, Reuter BK, Cicala C, McKnight W, Grisham MB, Cirino G (1994). "Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat". Gastroenterology. 107 (1): 172–179.
doi:
10.1016/0016-5085(94)90074-4.
PMID8020659.
^Wallace JL, Cirino G (1994). "The development of gastrointestinal-sparing anti-inflammatory drugs". Trends Pharmacol Sci. 15 (11): 405–406.
doi:
10.1016/0165-6147(94)90083-3.
PMID7855901.