The NSAID clometacin is an indometacin derivative. Clometacin is an analgesic drug that binds to human serum albumin (HSA) and inhibits the binding of indomethacin, warfarin, clofibrate and salicylic acid to HSA. Clometacin (DUPERAN) was approved in France in 1977. All preparations containing clometacin were withdrawn in 1987 due to their hepatotoxicity.

Lefetamine (L-SPA; L-1,2-diphenyl-l-dimethylaminoethane hydrochloride) is a synthetic compound with analgesic and anti-inflammatory action, introduced in clinical practice in Italy and Japan as ‘Santenol’. Santenol is available for oral (50 mg tablets1 and intramuscular (60 mg vials containing also lidocainel use. Animal studies have shown an analgesic effect and changes in EEG activity and O2 consumption of the nervous tissue. Lefetamine may be an opioid partial agonist. Lefetamine was first marketed in the 1940s as an opioid analgesic. Since withdrawal symptoms were observed during treatment, it became a controlled substance.

Vedaprofen is a PGE2 synthase inhibitor approved in Europe for the treatment of pain in horses and dogs.

Proquazon, a non-steroidal anti-inflammatory agent that was studied to use in the management of rheumatoid arthritis and osteoarthritis. The biochemical mechanism of action of proquazon via the inhibition of the core protein synthesis of proteoglycans and the secondary biosynthesis of the glucosamine.

Emorfazone is an analgetic agent that was developed by Morishita Pharmaceutical in Japan. The drug was tested for its ability to treat dental pain and inflammation in double blind study and was shown to be effective, however the exact mechanism of its action still remains unknown. Moreover, it is supposed that the effect is not mediated by interaction with opioids receptors or with prostaglandins synthesis.

Kebuzone is a cyclooxygenase inhibitor that was used for the treatment of different inflammatory conditions such as thrombophlebitis and rheumatoid arthritis. The current marketing status of the drug is unknown and supposed to be discontinued.

Feprazone is an anti-inflammatory compound developed for the treatment of such conditions as osteoarthritis, rheumatoid arthritis, rheumatic fever and gouty arthritis. The drug was tested in phase III of clinical trials, however its further faith is unknown.

Ibuproxam is a prodrug which metabolizes into ibuprofen and is therefore indicated for the treatment of pain and inflammation. Administration of oral ibuproxam resulted in a significantly higher plasma concentration than administration of an equal dose of ibuprofen after 45 minutes. Despite showing some promise as a NSAID ibuproxam does not appear to have been approved or marketed.

XIMOPROFEN, an arylpropionic acid group member, is a potent non-steroidal anti-inflammatory agent. Its efficacy was studied in several clinical trials in patients with rheumatic diseases.

Zaltoprofen is a non-steroidal anti-inflammatory drug approved in Japan for the treatment of lumbar pain, frozen shoulder, osteoarthritis, musculoskeletal pain, dental pain, post-operative pain. The main mechanism of action involves the inhibition of COX-2. Additional mechanism may be associated with the inhibitory effect of zaltoprofen on bradykinin-induced nociceptive responses that happens without blocking bradykinin receptors.