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 In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies.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.

Dihomo-gamma-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid that is mainly metabolized to an anti-inflammatory eicosanoid, prostaglandin (PG) E1, via the cyclooxygenase (COX) pathway. DGLA exists widely in the human body and daily animal-source foods. Concentrations of DGLA in the serum of atopic dermatitis patients are lower than those in healthy volunteers. DGLA suppressed clinical severity of skin lesions dose-dependently, with an increase in DGLA contents in phospholipids of skin, spleen, and plasma. Discontinuation of DGLA administration resulted in the onset of dermatitis and a decrease in DGLA contents in skin, spleen, and plasma. These findings indicate that oral administration of DGLA effectively prevents the development of atopic dermatitis in NC/Nga mice. DGLA may have an anti-atherosclerotic effect in apoE-deficient mice via PGE1 formation. As dihomo-γ-linolenic acid and arachidonic acid compete for processing by these oxidation enzymes, introduction of dihomo-γ-linolenic acid to platelets is correlated to suppression of arachidonic acid metabolites and promotion of dihomo-γ-linolenic acid metabolites such as PGE1, which produces an antithrombotic effect.

METHYLMETHIONINE (S-Methionine methyl sulfonium, SMMS) chloride is a derivative of methionine metabolism in some plants. Methylmethionine has therapeutic effects on gastrointestinal ulceration potentially via its ability to promote dermal fibroblast migration and growth. The natural derivative Methylmethionine is biosynthesized from L-methionine which is first converted to S-adenosylmethionine. The subsequent conversion, involving replacement of the adenosyl group by a methyl group is catalyzed by the enzyme methionine S-methyltransferase. Methylmethionine is particularly abundant in plants, being more abundant than methionine. S-Methylmethionine is sometimes referred to as vitamin U, but it is not considered a true vitamin. The term was coined in 1950 by Garnett Cheney for uncharacterized anti-ulcerogenic factors in raw cabbage juice that may help speed healing of peptic ulcers.

Tiazotic acid is an antioxidant. As tiazotic acid morpholinium salt it is marketed under the brand names Thiotriazoline, Tiokor among others in Russia, Ukraine, Uzbekistan as the treatment of ischemic heart diseases. It is proposed to be a hepatoprotective, wound-healing and antiviral agent. A comparative international multicenter randomized trial, assessed anti-anginal anti ischemic efficacy and safety of Trimetazidine (60 mg/d) and Thiotriazoline (600 mg/d) in symptomatic patients with chronic ischemic heart disease receiving the first line therapy. The study assessed the efficacy of the two drugs on total exercise duration, time to 1-mm ST segment depression, the number of angina attacks and nitroglycerin tablets consumed amount. Both drugs have demonstrated clinical efficacy equal for all primary and secondary endpoints. Thiotriazoline was also used for the he correction of hepatotoxicity during combined chemoradiotherapy for cancer patients.

Diphenpyramide is a non-steroidal anti-inflammatory compound, that has been studied in degenerative and inflammatory arthropathies treatment. In animal tests, Diphenpyramide showed anti-inflammatory action as powerful as that of indomethacin or phenylbutazone, with major peripheral analgesic, antipyretic and uricosuric properties. The therapeutic index was more favorable than that of the reference compounds. Diphenpyramide inhibits the synthesis of inflammatory prostaglandins and antagonizes the mediators of inflammation, but does not affect platelet aggregation or blood clotting. The anti-inflammatory action of diphenpyramide has been extensively proven in clinical trials in which patients with various inflammatory conditions, mainly of a musculoskeletal nature, were treated. The overall therapeutic efficacy was over 80% with a high proportion of osteoarthritis. In double-blind studies, the efficacy of Diphenpyramide was significantly better than that of acetylsalicylic acid or indomethacin in osteoarthritis and comparable with that of naproxen. Side-effects were seldom reported, were mild and transient and mainly of a gastrointestinal nature.

Proglumetacin (usually as the maleate salt, trade names Afloxan, Protaxon and Proxil) is a non-steroidal anti-inflammatory drug. Proglumetacin is indicated for the pain and inflammation associated with musculoskeletal and joint disorders. The action of proglumetacin maleate is qualitatively the same as that of indomethacin in vivo; that is, it inhibits cyclo-oxygenase in inflammatory sites.

Roxatidine is an histamine H2-receptor antagonist. Roxatidine is a potent and selective inhibitor of basal and stimulated gastric acid secretion through competitive blockade of H2-receptors. Total pepsin secretion is reduced in a dose-dependent manner. There is an independent mucosal protection action. Roxatidine is indicated for the treatment of peptic ulcer, gastro-oesophageal reflux disease, gastritis, upper gastrointestinal haemorrhage and Zollinger-Ellison syndrome also it can be used as a premedication before anaesthesia. Roxatidine possessed a robust estrogenic activity.

There is a little information about acetoxolone. It is known, that this drug is an acetyl derivative of the glycyrrhetinic acid, which is used to treat peptic ulcer.

Iobenzamic acid is a contrast medium, which was used for cholecystography under the name Osbil. It is assumed that the drug is no longer marketed.