Sivelestat is a neutrophil elastase inhibitor approved in Japan and the Republic of Korea for acute lung injury, including acute respiratory distress syndrome in patients with systemic inflammatory response syndrome. Sivelestat is marketed as Elaspol in Japan. Sivelestat competitively inhibited human neutrophil elastase (IC50 = 0.044 uM, Ki = 0.2 uM). It also inhibited leukocyte elastase obtained from rabbit, rat, hamster and mouse.

Gabexate is a synthetic protease inhibitor, was shown to be effective in treating patients with sepsis-associated disseminated intravascular coagulation in which tumor necrosis factor-alpha (TNF-alpha) plays a critical role. Gabexate mesylate is a drug marketed only in Italy and Japan and it is considered an essential drug in the treatment of acute pancreatitis. Gabexate is marketed under the brand name REMINARON among others in Japan. It relieves inflammatory symptoms in the pancreas by inhibiting various enzymes. It also improves organ disorders and bleeding tendency caused by blood clots in blood vessels by inhibiting blood coagulation. It is usually used to treat acute pancreatitis with deviation of proteolytic enzymes (such as trypsin, kallikrein and plasmin), acute exacerbation of chronic recurrent pancreatitis, acute pancreatitis after surgery and disseminated intravascular coagulation.

Perhexiline, 2-(2,2-dicyclohexylethyl)piperidine, is an anti-anginal drug. Perhexiline reduces fatty acid metabolism through the inhibition of carnitine palmitoyltransferase, the enzyme responsible for mitochondrial uptake of long-chain fatty acids. Perhexiline is used for reducing the frequency of moderate to severe attacks of angina pectoris due to coronary artery disease in patients who have not responded to other conventional therapy or in whom such therapy may be contraindicated. Heart Metabolics Limited is developing perhexiline for the treatment of hypertrophic cardiomyopathy

Phloroglucinol is an organic compound that is used in the synthesis of pharmaceuticals and explosives. Phloroglucinol is a phenol derivative with antispasmodic properties that is used primarily as a laboratory reagent. The mechanism of action is most likely based on the direct inhibition of the voltage-dependent calcium channels of smooth muscle; however, the modulation of prostaglandin or nitric oxide release has also been suggested. Although it has long been used in clinical practice as an antispasmodic for painful urogenital and gastrointestinal conditions, in an early study on anesthetized rats, phloroglucinol was found to be inactive toward the contraction of the duodenum, ileum and colon. Similarly, in anesthetized dogs, phloroglucinol plus trimethyl-phloroglucinol failed to antagonize acetylcholine-induced contraction of the colon. In parallel with animal studies, phloroglucinol plus trimethyl-phloroglucinol had no clear effects in humans on ascending and sigmoid colon hypermotility evoked by neostigmine. However in Irritable bowel syndrome (IBS) patients iv phloroglucinol effectively reduced postprandial rectosigmoid motility increases after a test meal, compared to placebo. In another study of IBS patients, phloroglucinol inhibited phasic contractions provoked by intrarectally injected glycerol, but it did not modify colonic tone. In an open-label study of 100 IBS patients selected according to the Rome II criteria, po 50 mg phloroglucinol was administered three times daily for two months. The 68 patients who completed the study reported significant improvement in abdominal pain, frequency of stools per day, urgency, passage of mucus per the rectum, sense of incomplete defecation and bloating. Nevertheless, straining was unchanged. Further, a multicenter, randomized, double-blind, placebo-controlled trial examined the effects of phloroglucinol/trimethylphloroglucinol (62.2 mg P plus 80 mg TMP three times daily) or placebo for 7 d in 307 IBS patients diagnosed using the Rome II criteria. The relative decrease in pain intensity and the responder rate were significantly higher in the P/TMP-treated group, compared to the placebo-treated group. Further, the treatment effect persisted up to the 7th day in a higher percentage of patients treated with P/TMP than in those treated with placebo.

Oxantel is a narrow-spectrum anthelmintic effective against whipworms in dogs and cats. It is ineffective against other roundworms, flukes, tapeworms or external parasites. Oxantel acts on the nervous system of the worms as inhibitors of acetylcholinesterase. Oxantel, a cholinergic anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm formation by P. gingivalis and disrupted established biofilms at concentrations below its MIC against planktonic cells. Oxantel was more effective against P. gingivalis in biofilm than metronidazole, a commonly used antibiotic for periodontitis. When oxantel was administrated to human beings for the treatment of trichuriasis, no drug reaction or side effects were reported, and the results of hematologic, biochemical and urinary examinations didn’t reveal any significant drug-related changes.

Garenoxacin is an antibacterial agent active against a range of aerobic Gram-positive and Gram-negative bacteria. It exerts its action by inhibiting bacterial DNA gyrase and topoisomerase IV. The drug was withdrawn from the market in Europe and was never approved in the USA. Garenoxacin is still marketed in Japan under the name Geninax.

Sitafloxacin hydrate (DU-6859a, Gracevit), a new-generation, broad-spectrum oral fluoroquinolone that is very active against many Gram-positive, Gram-negative and anaerobic clinical isolates, including strains resistant to other fluoroquinolones, was recently approved in Japan for the treatment of respiratory and urinary tract infections. This is a new quinolone oral antibacterial to inhibit DNA replication of bacteria at the time of infection, and shows antibacterial action. Sitafloxacin is active against methicillin-resistant staphylococci, Streptococcus pneumoniae and other streptococci with reduced susceptibility to levofloxacin and other quinolones and enterococci. Sitafloxacin has also demonstrated activity against clinical isolates of Klebsiella pneumoniae (including about 67% of strains producing extended-spectrum, beta-lactamases and resistant to ciprofloxacin), Enterobacter cloacae, Pseudomonas aeruginosa with some activity against quinolone-resistant strains and Acinetobacter baumannii. The in vitro activity against anaerobes is comparable to imipenem or metronidazole. Sitafloxacin showed dual inhibitory activity against both enzymes: Streptococcus pneumoniae DNA gyrase and topoisomerase IV.

Pixantrone is a novel anthracenedione. It is a weak inhibitor of topoisomerase II. Pixantrone directly alkylates DNA forming stable DNA adducts and cross-strand breaks. Pixuvri is approved for the treatment of adult patients with multiply relapsed or refractory aggressive Non-Hodgkin lymphomas. It is used for patients whose cancer does not respond or has returned after they have received other chemotherapy treatments. The most frequent AE were seen in the blood (mainly neutropaenia), gastrointestinal (nausea, abdominal pain, constipation) and respiratory systems (cough, dyspnea). No drug-drug interaction studies have been submitted and no drug interactions have been reported in human subjects

Pirmenol is an antiarrhythmic agent, which exhibits effects on the fast action potential similar to other class 1 membrane active antiarrhythmic agents. Pirmenol depresses not only the fast Na+ channel, but also others, such as the slow Ca2+ and K+ channels. Pirmenol had sevenfold lower affinity for glandular-type muscarinic receptors (M3) than for cardiac-type muscarinic receptors (M2). This medicine regulates disturbed pulse by acting on the cardiac muscle. Usually, used for treatment of tachyarrhythmia (ventricular). The most commonly reported adverse reactions include constipation, discomfort in stomach, difficulty in urination (urinary retention), headache, insomnia, bitterness in the mouth, nausea, dry mouth and palpitation. Lidocaine, procainamide and quinidine a greater degree of arrhythmia conversion occurred when dosed 15 min after pirmenol than when these agents were dosed alone.

3-Aminopropionitrile (Beta-amino-propionitrile, BAPN) is a toxic constituent from lathyrus plants. BAPN found in lathyrus odoratus (our more common garden sweet pea plant) is thought to be responsible for osteolathyrism due to irreversible inhibition of lysyl oxidase (LOX), an enzyme necessary for the covalent cross-linking of tropocollagen molecules during the maturation of mature collagen. BAPN demonstrated in antimetastatic and antimyelofibrotic activity in vivo due to inhibition of LOX.