Allopurinol is a xanthine oxidase inhibitor used to decrease high blood uric acid levels. Allopurinol is specifically used to prevent gout, prevent specific types of kidney stones, and for the high uric acid levels that can occur with chemotherapy. Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. Allopurinol is a structural analog of the natural purine base, hypoxanthine. It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in man. Allopurinol is metabolized to the corresponding xanthine analog, oxypurinol (Allopurinol), which also is an inhibitor of xanthine oxidase. Allopurinol is taken by mouth or injected into a vein. Common side effects, when used by mouth, include itchiness and rash. Common side effects when used by injection include vomiting and kidney problems.

Probenecid is the prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Probenecid is used for treatment of the hyperuricemia associated with gout and gouty arthritis. Probenecid is a uricosuric and renal tubular blocking agent. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. Probenecid inhibits the tubular secretion of penicillin and usually increases penicillin plasma levels by any route the antibiotic is given. A 2-fold to 4-fold elevation has been demonstrated for various penicillins. Probenecid decreases both hepatic and renal excretion of sulfobromophthalein (BSP). The tubular reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals. Probenecid does not influence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline, or neomycin.

Colchicine is an alkaloid obtained from the plant colchicum autumnale (also known as "meadow saffron"). Colchicine is an alternative medication for those unable to tolerate NSAIDs in gout. Mechanism of action of colchicine is inhibition of microtubule polymerization by binding to tubulin. Availability of tubulin is essential to mitosis, so colchicine effectively unctions as a "mitotic poison" or spindle poison.

Arhalofenate is a uricosuric drug which lowers serum urate by blocking its reabsorption by the proximal tubules of the kidney. Arhalofenate activity is mediated by inhibition of URAT1, OAT4 and OAT10. Additionally, arhalofenate has been suggested to exert potent anti-inflammatory activity. Arhalofenate has completed Phase 2 and is ready to advance to Phase 3 as a novel potential treatment for gout. The drug was also tested in patients with type 2 diabetes mellitus (phase III study), where it demonstrated its ability to lower glucose level, acting as a selective, partial PPAR-gamma agonist. However, the development of arhalofenate as an anti-diabetic drug was terminated.

Y-700 (Niraxostat or 1-[3-Cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid) is an inhibitor of xanthine oxidoreductase. Y-700 demonstrated high oral bioavailability being predominantly eliminated via the liver. It potently reduces serum uric acid levels. Y-700 was in clinical trials for the treatment of gout.

Zoxazolamine is a centrally acting muscle relaxant. It decreased striatal dopamine metabolism without affecting striatal dopamine concentrations. More specifically, Zoxazolamine was shown to decrease striatal dopamine turnover without directly affecting dopamine synthesis, catabolism, reuptake, or release. It is the IK(Ca) channel opener. It was approved for the relief of muscle spasm in conditions such as musculoskeletal disorders and neurological diseases. Later, it was submitted for the drug's use as a uricosuric agent to treat gout. It was withdrawn from the market due to hepatotoxicity.

Phenylbutazone is an anti-inflammatory drug, which binds to and inactivates cyclooxygenases and prostacyclin synthase through peroxide (H2O2) mediated deactivation. The reduced production of prostaglandin leads to reduced inflammation of the surrounding tissues. Phenylbutazone was marked under the brand name butazolidin for the treatment rheumatoid arthritis and gout, but then this usage was discontinued. In addition, phenylbutazone is used in UK for the treatment of ankylosing spondylitis, but only in those cases, when other therapies are unsuitable.

Etebenecid is a uricosuric agent, lower uric acid levels in the body by increasing the elimination of uric acid by the kidneys, also inhibits penicillin tubular secretion. It is useful in the interval treatment of gout. As with other uricosuric drugs, etebenecid may provoke acute gouty attacks in the early stages of treatment, and colchicine should be given during the first 6 weeks of treatment. It caused dyspepsia and diarrhea less frequently than probenecid and sulphinpyrazone. Several patients reported drowsiness while taking etebenecid in the treatment of gout, but no other side-effects were noted. Etebenecid should be given with care to patients with a history of uric acid calculi or of renal colic.

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.

Benzbromarone (INN) is a uricosuric agent and non-competitive inhibitor of xanthine oxidase used in the treatment of gout, especially when the first line treatment, allopurinol, fails or produces intolerable adverse effects. It is structurally related to the antiarrhythmic amiodarone. Benzbromarone was introduced in the 1970s and was viewed as having few associated serious adverse reactions. It was registered in about 20 countries throughout Asia, South America and Europe. In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies. The withdrawal has greatly limited its availability around the world and increased difficulty in accessing it in other countries where it has never been available. Standard dosages of benzbromarone (100 mg/day) tend to produce greater hypouricaemic effects than standard doses of allopourinol (300 mg/day) or probenecid (1000 mg/day). Adverse effects associated with benzbromarone are relatively infrequent but potentially severe. Four cases of benzbromarone-induced hepatotoxicity were identified from primary literature, and eleven cases have been reported by Sanofi-Synthélabo but details are not available in the public domain. Only one of the four publicly published cases demonstrated a clear relationship between the drug and liver injury as demonstrated by rechallenge. The other three cases lacked incontrovertible evidence to support a diagnosis of benzbromarone-induced hepatotoxicity. If all the reported cases are assumed to be due to benzbromarone, the estimated risk of hepatotoxicity in Europe was approximately 1 in 17 000 patients but may be higher in Japan. Benzbromarone is a very potent inhibitor of CYP2C9. The mechanism of benzbromarone hepatotoxicity is believed to be due to its hepatic metabolism by CYP2C9 and possible effects of the parent compound or its metabolites on mitochondrial function. Benzbromarone is a benzofuran and shares structural similarities with benzarone and amiodarone, all three of which affect mitochondrial function.