Efipladib is an inhibitor of cytosolic phospholipase A2 alpha both in vitro and in vivo. It is able to relieve inflammatory pain in animal model. Additionally, efipladib exerts antitumor potential. Efipladib was in clinical trials for the treatment of asthma and arthritis however its development has been discontinued.

Fluprofen was invented as an analgesic and anti-inflammatory agent. However, information about the current use of this drug is not available.

Cinnofuradione is a cinnoline derivative with analgesic properties. It was patented in 1954 and was claimed to be useful in combatting inflammation and rheumatism.

Tiflamizole is a fluorinated diarylamidazole derivative patented by du Pont de Nemours, E. I., and Co. as an anti-inflammatory agent. Tiflamizole acts as a non-steroidal anti-inflammatory drug, that exerts potent inhibition of prostaglandin synthesis and exhibits anti-inflammatory, antipyretic, and analgesic activity in animal studies. Preliminary studies in animals and man have shown that Tiflamizole is rapidly absorbed from the gastrointestinal tract, is highly protein-bound, and is slowly excreted. Toxicity studies in animals focused on the gastrointestinal tract. Short-term toxicity studies in rats indicated that the margin of safety of Tiflamizole is greater than that for piroxicam, ibuprofen, or sulindac.

Pinadoline is a competitive PGE2 antagonist. It is an analgesic agent. Pinadoline demonstrated the antinociceptive activity in the rat using the writhing and the formalin tests. In the writhing test, pinadoline was significantly more potent than inhibitors of PG synthesis, but less potent than opiate analgesics. In the formalin test, pinadoline appeared less active than aspirin and ibuprofen and more active than acetaminophen. Pinadoline does not possess the antiinflammatory activity of aspirin and ibuprofen and may be more like acetaminophen, which had diminished antiinflammatory activity. At high concentrations, pinadoline is a non-competitive antagonist of serotonin in guinea-pig ileum.

Tofetridine is an analgesic agent.

Naftypramide is a nonsteroidal anti-inflammatory drug. It was used in the treatment of gynecological inflammatory diseases.

Mexoprofen was studied as an analgesic agent. This compound has never been marketed.

RGH-896 (radiprodi) is orally active and selective NMDA NR2B antagonist, a potential therapeutic agent in treatment of neuropathic pain and possibly other chronic pain conditions. It blocks pain signaling without interacting with other NMDA receptor subtypes thus potentially improving therapeutic index and side effect profile. RGH-896 is the first of this group and is currently in early clinical development. Forest and Richter initiated a Phase IIb study in neuropathic pain in the United Stated in the second half of 2006. The drug did not produce significant reductions in patient-reported pain scores for all the dosages tested. Forest says that it and Gedeon Richter will review the findings before making a decision about the further development of radiprodil. In addition to neuropathic pain, the companies intend to investigate various other pain conditions and possibly CNS indications not related to pain. Forest will pay Richter undisclosed upfront and milestone payments in addition to royalties and will have exclusive rights in the U.S. and Canada. The two companies will jointly fund the development program. RGH-896 has patent applications that provide patent protection until at least 2022.

Camobucol is a novel, orally active, phenolic antioxidant and anti-inflammatory compound with antirheumatic properties. Camobucol exhibited potent antioxidant activity toward lipid peroxides in vitro and displayed enhanced cellular uptake relative to a structurally related drug, probucol. This resulted in potent inhibition of cellular levels of reactive oxygen species in multiple cell types. Camobucol selectively inhibited tumor necrosis factor (TNF)-alpha-inducible levels of the redox-sensitive genes, vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, with less inhibition of E-selectin, and no effect on intracellular adhesion molecule-1 expression in endothelial cells. In addition, Camobucol inhibited cytokine-induced levels of monocyte chemoattractant protein-1, interleukin (IL)-6, and IL-8 from endothelial cells and human fibroblast-like synoviocytes as well as lipopolysaccharide-induced release of TNF-alpha, IL-1beta, and IL-6 from human peripheral blood mononuclear cells. Camobucol did not inhibit TNF-alpha-induced nuclear translocation of nuclear factor of the kappa-enhancer in B cells (NF-kappaB), suggesting that the mechanism of action is independent of this redox-sensitive transcription factor.