Alimadol, an opioid analgesic similar to methadone that has never been marketed, and is a DEA controlled substance.

Crotetamide, is the main component of the drug Prethcamide, which is a respiratory stimulant to produce arousal from drug-induced depression. Prethcamide produces a marked increase in ventilation, primarily as a result of increased tidal volume, with minimal increases in respiratory rate. Prethcamide is marketed for parenteral and oral administration to humans in several European and South American countries but is not approved by the U.S. Food and Drug Administration for use in either human or veterinary medicine in the United States. Prethcamide is banned by several sports governing bodies, including the International Olympic Committee and the International Amateur Athletic Federation, because of its potential to stimulate performance of athletes.

Etofenamate is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of joint and muscular pain.

Acexamic acid (N-acetyl-amino-6-hexanoic acid) is a drug used as a cicatrization helper. Some studies show that the acexamic acid prevents the formation the connective inflamed tissue and enables its healing. The association from acexamic acid with zinc, zinc acexamate, has been used in the treatment of gastric and duodenal ulcer and in the prevention of gastric ulcer induced by nonsteroidal anti-inflammatory drugs.

PARSALMIDE, a benzamide derivative, is an anti-inflammatory drug with analgesic effect. It may also possess anxiolytic and tranquilizing properties. PARSALMIDE was commercialized in Italy until 1985 with the brand name of Synovial®, that was widely used to treat arthritic patients.

Butanixin (2-(p-butanilino)nicotinic acid) is a compound with analgesic, antipyretic and anti-inflammatory activity.

Floctafenine is an analgesic agent used for the treatment of pain. The drug exerts its anti-inflammatory action by inhibiting COX-1 and COX-2, with a slight preference towards COX-1. Floctafenine is marketed in Canada under the name Floctafenine and it is withdrawn in Europe (Idarac Brand name).

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.

Fenclozic acid emerged in the late 1960s as a promising carboxylic acid non-steroidal anti-inflammatory drug candidate that demonstrated potent anti-inflammatory, anti-pyretic and analgesic properties. Whole body autoradiography showed fenclozic acid distribution into all tissues except the brain, with radioactivity still detectable in blood, kidney and liver at 72 h post-dose. Fenclozic acid was compared with aspirin in a double-blind, crossover trial in patients with rheumatoid arthritis. It was concluded that fenclozic acid afforded symptomatic relief and was comparable to aspirin. Unfortunately, hepatotoxicity was observed in subsequent trials and the drug was withdrawn from the clinic.

Bufezolac is a non-steroidal anti-inflammatory drug (NSAID). In the mouse, BUFEZOLAC was 30 times less active than indomethacin in Koster's test, but it was 13 times less toxic than the reference drugs. Bufezolac appeared to be as active as indomethacin in the various tests performed: Randall and Selitto's test for analgesic activity, hyperthermic rat, experimental models of inflammation (UV erythema, carrageenin-induced oedema, cotton granuloma, adjuvant-induced arthritis). In vitro, its inhibition of prostaglandin-synthetase in the guinea-pig lung was appreciably more powerful than that of indomethacin. Like all potent non-steroid anti-inflammatory drugs it has ulcerogenic activity, similar to that of indomethacin, which accounts for its acute oral toxicity in the rat. The activity Bufezolac is either the same as (antipyretic action) or inferior to (analgesic and anti-inflammatory activity and inhibition of prostaglandin-synthetase) that of indomethacin, but always markedly superior to that of phenylbutazone.