Firocoxib is a selective COX-2 inhibitor which was approved by FDA and EMEA for the treatment of osteoarthritis and postoperative pain in dogs (Previcox trade name) and horses (Equioxx trade name). The drug is not for human use.

Flunixin meglumine is a potent, non-narcotic, non-steroidal, analgesic agent with anti-inflammatory and anti-pyretic activity was approved to use in horses, cattle and pigs. In horses it is recommended for the alleviation of inflammation and pain associated with musculoskeletal disorders. It is also recommended for the alleviation of visceral pain associated with colic. In the cattle: it is indicated for the control of pyrexia associated with bovine respiratory disease, endotoxemia and acute bovine mastitis. It is also indicated for the control of inflammation in endotoxemia. Flunixin persists in inflammatory tissues and is associated with anti-inflammatory properties which extend well beyond the period associated with detectable plasma drug concentration. Flunixin meglumine is classified as a carboxylic acid. Its mechanism of action is believed to be primarily via the inhibition of cyclooxygenase (COX) enzymes. This inhibition results in decreased formation of cyclooxygenase-derived eicosanoids involved in the pathophysiology of inflammation, such as thromboxanes and prostaglandins.

Glucosamine is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of the polysaccharides chitosan and chitin, which compose the exoskeletons of crustaceans and other arthropods, as well as the cell walls of fungi and many higher organisms. Glucosamine is one of the most abundant monosaccharides. It is produced commercially by the hydrolysis of crustacean exoskeletons or, less commonly, by fermentation of a grain such as corn or wheat. Oral glucosamine is a dietary supplement and is not a pharmaceutical drug. It is illegal in the US to market any dietary supplement as a treatment for any disease or condition. Glucosamine is marketed to support the structure and function of joints, and the marketing is targeted to people suffering from osteoarthritis. Commonly sold forms of glucosamine are glucosamine sulfate, glucosamine hydrochloride, and N-acetylglucosamine. Of the three commonly available forms of glucosamine, only glucosamine sulfate is given a "likely effective" rating for treating osteoarthritis. Glucosamine is often sold in combination with other supplements such as chondroitin sulfate and methylsulfonylmethane. Glucosamine, along with commonly used chondroitin, is not routinely prescribed to treat people who have symptomatic osteoarthritis of the knee, as there is insufficient evidence that this treatment is helpful. One clinical study over three years showed that glucosamine in doses of 1500 mg per day is safe to use. Glucosamine with or without chondroitin elevates the international normalized ratio (INR) in individuals who are taking the blood thinner, warfarin. It may also interfere with the efficacy of chemotherapy for treating cancer symptoms. Adverse effects may include stomach upset, constipation, diarrhea, headache, and rash. There are case reports of people who have chronic liver disease and a worsening of their condition with glucosamine supplementation. Glucosamine is naturally present in the shells of shellfish, animal bones, bone marrow, and fungi. D-Glucosamine is made naturally in the form of glucosamine-6-phosphate, and is the biochemical precursor of all nitrogen-containing sugars. Specifically in humans, glucosamine-6-phosphate is synthesized from fructose 6-phosphate and glutamine by glutamine—fructose-6-phosphate transaminase as the first step of the hexosamine biosynthesis pathway. The end-product of this pathway is uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is then used for making glycosaminoglycans, proteoglycans, and glycolipids. As the formation of glucosamine-6-phosphate is the first step for the synthesis of these products, glucosamine may be important in regulating their production; however, the way that the hexosamine biosynthesis pathway is actually regulated, and whether this could be involved in contributing to human disease remains unclear.

Acemetacin is a non-steroidal anti-inflammatory drug used for the treatment of osteoarthritis, rheumatoid arthritis, lower back pain, and relieving post-operative pain. It is manufactured by Merck KGaA under the tradename Emflex and is available in the UK as a prescription-only drug. Other brand names for acemetacin include Rheutrop (Austria), Acemetadoc, Acephlogont, Azeat, Rantudil (Germany, Hungary, Mexico, Portugal, Turkey), Gamespir (Greece), Oldan, Reudol (Spain), Tilur (Switzerland), Ost-map (Egypt). Acemetacin is a glycolic acid ester of indomethacin. The pharmacological activity resulting from acemetacin administration in man is derived from the presence of both acemetacin and indomethacin. The precise pharmacological mode of action of acemetacin is not known. However, unlike other NSAIDs, acemetacin is only a relatively weak inhibitor of prostaglandin synthetase. Prostaglandins are known to have an antisecretory and cytoprotective effect on the gastric mucosa. Acemetacin shows activity in many of the established in vitro tests of anti-inflammatory activity including inhibition of the release of a number of mediators of inflammation. Acemetacin is well absorbed after oral administration. Its major metabolite is indomethacin, which, after repeated administration is present at levels in excess of those of acemetacin. Acemetacin is bound to plasma protein to a slightly lesser extent than indomethacin and has a relatively short plasma elimination half-life. It is eliminated by both hepatic and renal mechanisms. The pharmacokinetics appear to be linear at recommended therapeutic doses, unaffected by moderate renal or hepatic impairment, and unchanged in the elderly.

Alclofenac (Preservex) is a non-steroidal anti-inflammatory agent advocated for use in rheumatoid arthritis, degenerative joint disease and ankylosing spondylitis. Aceclofenac has little pharmacological activity itself; its main mode of action is through its metabolites which include diclofenac and 4’-hydroxy diclofenac. Skin rash is the most frequent side-effect, which in a small proportion of affected patients may be associated with systemic effects. A cutaneous reaction appears to be more likely in patients with a history of previous allergy to penicillin and other drugs. In June 2013 was told about the new contraindications and warnings for diclofenac. This was after a review by European regulators concluded that the risk of arterial thrombotic events (myocardial infarction; stroke) with diclofenac is greater than with other non-selective NSAIDs and similar to the COX-2 inhibitors.

Tenidap ([Z]-5-chloro-2,3-dihydro-3-[hydroxy-2-thienylmethylene]-2-oxo-1H-indole-1-carboxamide) is an oxindole derivative, a COX/5-LOX inhibitor and cytokine-modulating anti-inflammatory drug candidate that was under development by Pfizer as a promising potential treatment for rheumatoid arthritis. Tenidap shows potent inhibition of cyclooxygenase in vitro, that is of several magnitudes greater than 5-lipoxygenase inhibition. Lipoxygenase inhibition, however, has been difficult to document in vivo because Tenidap is highly protein bound and free drug concentrations are below those necessary for 5-lipoxygenase inhibition. However, several in-vitro activities distinguish Tenidap from conventional cyclooxygenase inhibitors. As shown with stimulated human neutrophils, tenidap inhibits activation of collagenase, lysosomal enzyme secretion, and superoxide generation, as well as aggregation and adhesion to endothelium. Furthermore, unlike Non-steroidal anti-inflammatory drugs (NSAIDs), it lowers circulating C-reactive protein (CRP) concentrations by a magnitude equivalent to hydroxychloroquine and auranofin. This result suggests an effect on the synthesis and/or release of the cytokines known to induce the acute-phase protein response-namely, IL-1, IL-6, and TNF-alpha. Tenidap, like existing second-line drugs, lowers serum IL-6 concentrations, a property not shared by NSAIDs The cytokine inhibitory effect also includes reduced in-vitro concentrations of TNF-alpha and IL-1 from both RA synovium and peripheral blood mononuclear cells. There is no immunosuppressive effect of Tenidap in either animal or clinical studies. In clinical studies. The comparisons between tenidap and other second-line agents show that Tenidap produced a faster reduction in CRP than Auranofin. The rate of withdrawal because of inefficacy was similar (18-20%) in Auranofin and Tenidap groups. The quality of life using the arthritis impact measurement scales has also been assessed Scores were better with tenidap than with NSAID monotherapy, but equivalent to the second line plus NSAID combinations. Tenidap is registered in the United States, Netherlands, and Italy but is not marketed because marketing approval was rejected by the FDA in 1996 due to liver and kidney toxicity, which was attributed to metabolites of the drug with a thiophene moiety that caused oxidative damage.

Droxicam is a nonsteroidal anti-inflammatory drug that is a pro-drug of piroxicam. The mechanism of action of droxicam, as well as that of piroxicam, is that of inhibition of prostaglandin biosynthesis. Droxicam acts by inhibition of PGE2. Although it belongs to the oxicam family, it is characterised by being a pro-drug of piroxicam, the molecule undergoing conversion by hydrolysis once dissolved in the digestive tract. Droxicam was used for the relief of pain and inflammation in musculoskeletal disorders such as rheumatoid arthritis and osteoarthritis. Droxicam possesses considerable analgesic activity, of equal magnitude to that of piroxicam and notably greater than that of acetylsalicylic acid, dipyrone, phenylbutazone and isoxicam. The antipyretic activity of droxicam, studied by means of different tests, has shown itself to be clearly superior to that of acetylsalicylic acid, dipyrone and 4-aminoantipyrine. Droxicam acts as an inhibitor of ex vivo platelet aggregation in the dog. However, owing to hepatotoxicity, droxicam was withdrawn in many countries.

3-hydroxy-2-phenylcinchoninic acid (also known as oxycinchophen or earlier as HPC) was known as antidiuretic and has been specially found useful in cases of diabetes insipidus. Clinical studies of HPC revealed that this compound reduces water output in cases of diabetes insipidus, and this was reached not by direct action on the water reabsorbing element in the tubules of the kidney, but rather by the mediation of HPC on the pituitary system in the production of the antidiuretic hormone therein. The effect of HPC upon fever and arthritis on patients with rheumatic fever was dramatic. In addition, HPC cannot be considered as an antipyretic, but rather HPC should be considered as enhancing ins some way the output or activity of adrenal cortical hormones. HPC was shown rather toxic (toxic reaction were presented in 20 % of tested patients). That is why the development of this drug was stopped and is become study its derivatives.

Azapropazone is a non-steroidal anti-inflammatory drug. It is indicated for use in the treatment of rheumatoid arthritis, osteo-arthritis and gout. Gastro-intestinal disturbances, allergic skin rashes and photosensitivity, headache, vertigo, oedema and kidney impairment may occur. Gastro-intestinal bleeding and angioedema have been reported. Pre-treatment with this drug failed to modify plasma concentrations of phenobarbitone. Brain levels of imipramine or desmethyl imipramine were unaffected 60 minutes after oral administration of imipramine.

Lumiracoxib is a COX-2 selective inhibitor non-steroidal anti-inflammatory drug. On August 11, 2007, Australia's Therapeutic Goods Administration (TGA, the Australian equivalent of the FDA) cancelled the registration of lumiracoxib in Australia due to concerns that it may cause liver failure. New Zealand and Canada have also followed suit in recalling the drug. It has never been approved for use in the United States. Lumiracoxib has a different structure from the standard COX-2 inhibitors (e.g. celecoxib). It more closely resembles the structure of diclofenac (one chlorine substituted by fluorine, the phenylacetic acid has another methyl group in meta position), making it a member of the arylalkanoic acid family of NSAIDs. It binds to a different site on the COX-2 receptor than the standard COX-2 inhibitors. It displays extremely high COX-2 selectivity. The mechanism of action of lumiracoxib is due to inhibition of prostaglandin synthesis via inhibition of cyclooygenase-2 (COX-2). Lumiracoxib does not inhibit COX-1 at therapeutic concentrations. Lumiracoxib is used for the acute and chronic treatment of the signs and symptoms of osteoarthritis of the knee in adults.