Apadoline [RP 60180, RP 60180A, RPR 60180] is a κ-opioid receptor agonist which was undergoing phase II clinical trials with Aventis Pharma for the treatment of pain.

Nicotredole (Tryptamide), similarly to ibuprofen and piroxicam, shows anti-inflammatory and analgesic properties. Tryptamide reversed pyrogen-induced hyperthermia in rats, elicited analgesic effects in rats, but not in mice, prolonged the time of hexobarbital sleep in rats and inhibited locomotor activity in rats and mice. Tryptamide has not elicited side effects on the circulatory system of rats and cats.

Bardoxolone methyl, the C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) known as CDDO-Me or RTA 402, is one of the derivatives of synthetic triterpenoids. Bardoxolone methyl directly blocks IKKbeta activity and thereby the NF-kappaB pathway by interacting with Cys-179 in the IKKbeta activation loop. Binding of bardoxolone methyl to Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) disrupts its critical cysteine residues, leading to the release of the nuclear factor erythroid 2-related factor 2 (Nrf2), which hinders its ubiquitination and finally leads to its stabilization and nuclear translocation. In the nucleus, Nrf2 activates the transcription of phase 2 response genes, leading to a coordinated antioxidant and anti-inflammatory response. In addition, it acts as an antagonist of the peroxisome proliferator-activated receptor gamma. Through Keap1/Nrf2 and nuclear factor-κB pathways, this agent can modulate the activities of a number of important proteins that regulate inflammation, redox balance, cell proliferation and programmed cell death. This agent is generally well tolerated, but it may increase adverse cardiovascular events. Presently, it is being further tested for the treatment of patients with chronic kidney disease, cancer, and pulmonary arterial hypertension.

Lonaprofen is an analgesic, antipyretic and anti-inflammatory agent.

Lofemizole is a non-steroidal anti-inflammatory drug. Lofemizole has proved to possess an interesting antiphlogistic activity in both animals and humans, associated with a favorable gastric and systemic tolerability.

Lobuprofen is an ester type analgesic, in which the acid moiety (ibuprofen) has peripheral analgesic activity and the alcohol moiety (mCPPol) has central analgesic activity.

Clobenetine is benzomorphan derivative developed by Boehringer-Ingelheim. Clobenetine acts as a sodium channel blocker and displaces radioligand from neurotoxin receptor site 2 of the Na(+) channel in rat brain synaptosomes with IC50 of 49 nM. The IC50 value for the inactivated Na(+) channels was much lower than for Na(+) channels in the resting state. In animal models, clobenetine reduced lesion size in mice and rats when administered 5 min after permanent focal cerebral ischemia at doses that did not impair motor coordination. Clobenetine produced significant analgesic and anti-hyperalgesic effects in the rat model of arthritis, induced by complete Freund's adjuvant. In the early 2000s, the compound was investigated in phase II clinical trial for the treatment of thromboembolic stroke, but no results were reported.

Ecopladib) is a sub-micromolar inhibitor of cytosolic phospholipase A2α (cPLA2α, type IVA phospholipase). Inhibitors of cPLA2alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. It displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.

Lexofenac is an ibufenac derivative. It was developed as anti-inflammatory and analgesic agent.

Clofenamic acid is a derivative of anthranilic acid, discovered by Parke-Davis. It possesses anti-inflammatory activity in the carrageenan-induced rat foot edema test.