Carmofur, also known as 5-fluoro-N-hexyl-2,4-dioxo-pyrimidine-1-carboxamide and as 1-hexylcarbamoyl-5-fluorouracil, is a pyrimidine analogue which acts as an antineoplastic agent through inhibition of thymidylate synthase. It has been used in the treatment of breast and colorectal cancer. Carmofur is approved in Japan for the treatment of cancer.

Octopamine is an organic chemical closely related to norepinephrine. In many types of invertebrates it functions as a neurotransmitter. Octopamine is known to exert adrenergic effects in mammals although specific octopamine receptors have been cloned only in invertebrates. It has been shown that octopamine can stimulate alpha(2)-adrenoceptors (ARs) in Chinese hamster ovary cells transfected with human alpha(2)-ARs. Octopamine stimulates lipolysis through beta(3)-rather than beta(1)-or beta(2)-AR activation in white adipocytes from different mammalian species. Octopamine activates only beta(3)-ARs and is devoid of alpha(2)-adrenergic agonism. Thus, octopamine could be considered as an endogenous selective beta(3)-AR agonist. In humans Octopamine is a trace amine found endogenously in the human brain where it interacts with signalling of catecholamines; it is structurally similar to synephrine and tyramine, being a metabolite of the latter (via dopamine β-hydroxylase) and substrate for the synthesis of the former (via phenethanolamine N-methyltransferase[3]) while being perhaps the closest in structure to noradrenaline. Octopamine is found in the bitter orange similar to many biogenic amines related to L-tyrosine that are used as dietary supplements, this includes synephrine and hordenine. p-Octopamine HCl (Norphen) was studied in the late 1960’s and 1970’s as a drug for the treatment of hypotensive regulatory and circulatory disorders. Octopamine was used as a nootropic. All optical isomers (enantiomers) of octopamine are on the World Anti-Doping Agency (WADA) 2014 list of substances prohibited in competition.

Benserazide is a peripherally-acting aromatic L-amino acid decarboxylase (AADC) or DOPA decarboxylase inhibitor. Benserazide is only used in conjunction with L-dopa for the treatment of Parkinson's disease under the brand name Madopar in the UK. Madopar HBS (125 mg) is a controlled-release dosage form with 100 mg L-dopa and 25 mg benserazide.

Canrenone, a spironolactone metabolite, is a mineralocorticoid receptor antagonist. Canrenone is used as a diuretic in Europe and, in particular, in Italy under brand name Luvion. Luvion is a tablet for oral application which is effective for the treatment Hyperaldosteronism primary, secondary hyperaldosteronism from edematous states ( heart failure congestive, cirrhosis of the liver in phase ascites, nephrotic syndrome) and arterial hypertension essential where other therapies were not sufficiently effective or tolerate. In addition was suggested that canrenone might represent an effective therapy for idiopathic post-puberal hirsutism and it normalizds the cardiac response to the postural challenge in patients with preascitic cirrhosis. Canrenone seems to be effective in reducing blood pressure in patients with metabolic syndrome. Moreover, canrenone seems also to improve MPO, Lp(a), and metalloproteinases in these patients.

Nitrendipine is a calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, nitrendipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

Methylchromone (3-methylchromone) is the first synthetic chromone to be used clinically. It has both antispasmodic and coronary vasodilator actions. It was recommended for the treatment of angina pectoris but it doesn’t produce any remarkable improvements and its clinical use has been discontinued. Osteomalacia case caused by the ingestion of 3-methylchromone was reported. 3-methylchromone was used in ureteral lithiasis and gravels. 3-methylchromone stated to have better vitamin K activity.

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

Formestane (trade name Lentaron) is a type I, steroidal, selective aromatase inhibitor used in the treatment of estrogen receptor-positive breast cancer in postmenopausal women. Formestane has poor oral bioavailability and thus must be administered fortnightly (bi-weekly) by intramuscular injection. Formestane is a second generation, irreversible, steroidal aromatase inhibitor. It inhibits the aromatase enzyme responsible for converting androgens to estrogens, thereby preventing estrogen production. Estrogen-sensitive breast cancer cells depend on estrogen for viability. Thus removal of estrogen from the body can be an effective treatment for hormone-sensitive breast cancers. Common side effects associated with the use of an aromatase inhibitor include hot flashes, joint pain, weakness, fatigue, mood changes, depression, high blood pressure, swelling of the arms/legs, and headache. Aromatase inhibitors may also decrease bone mineral density, which may lead to osteoporosis and an increase in fractures in susceptible patients. Formestane was the first selective aromatase inhibitor to be developed as a prescription drug, first appearing in Europe during the mid-1990s under the Lentaron Depot brand name. With the emergence of newer and more effective aromatase inhibitors, however, formestane soon lost market presence at a rapid rate. Most of the initial Lentaron preparations have since been discontinued. Currently, formestane (categorized as an anti-estrogenic agent) is prohibited from use in sports in accordance with the regulations of the World Anti-Doping Agency. The drug remains available today, but only in a small number of nations. This includes Austria, Brazil, Czech Republic, Hong Kong, and Turkey.

Lonidamine is a derivative of the indazole-3-carboxylic acid, with limited antineoplastic activity as a single agent but with exceptional potential in modulating the activities of conventional chemotherapeutic agents such as N-mustard alkylating agents and anthracyclines as well as hyperthermia, radiation therapy and photodynamic therapy. The most critical property of Lonidamine is its selective activity against a broad range of tumors with little to no effect on normal tissues provided that doses are below a threshold level of ~400 mg/m^2 (oral or i.v. doses). Selective effects of Lonidamine on tumors compared to other potential targets probably result from the dependence of most tumors on glycolytic metabolism, but the exact mechanism of specificity is still not fully known. Current evidence indicates that Lonidamine inhibits lactate export by the proton-linked monocarboxylate transporter(s) (MCT) and pyruvate uptake into mitochondria via the mitochondrial pyruvate carrier (MPC), whereas inhibition of respiration involves both diminished mitochondrial uptake of pyruvate via the MPC as well as inhibition of the mitochondrial electron-transport chain at Complex II and perhaps also Complex I, in both instances at the ubiquinone reduction step. There is also evidence that the drug may indirectly inhibit hexokinase as well as possibly other glycolytic and pentose shunt enzymes as a result of cytosolic acidification. Key problems that remain to be addressed are the production of Lonidamine under GMP conditions since Angelini Pharmaceuticals in Rome, Italy, the sole commercial source of this drug, stopped producing it in 2006. In addition, utilization of Lonidamine in the US requires IND approval by the FDA, which has previously been granted for a number of clinical trials. Finally, even though LND is a potent enhancer of the activity of a number of potent anti-cancer agents, potentially less toxic (and patentable) “targeted-tumor agents” are replacing traditional chemotherapy. Another problem remaining to be addressed is the limited solubility of Lonidamine at neutral pH. Oral delivery has led to variable results; more soluble derivatives that can be administered by the intravenous administration are needed to accurately control the dosing schedules.

Tetrandrine, isolated from the root of Stephania tetrandra S Moore, is a traditional Chinese clinical agent for silicosis, autoimmune disorders, inflammatory pulmonary diseases, cardiovascular diseases and hypertension. Tetrandrine is a potent MDR-reversing agent and is an ABCB1/ABCC1 inhibitor. Tetrandrine (CBT-1) is being developed by CBA Pharma, as an adjunctive therapy to chemotherapy in various cancer types with multiple drug resistance (MDR), including acute myelogenous leukemia , Breast, Non-Hodgkin’s Lymphoma, Hodgkin’s disease, Non-Small Cell Lung Cancer, Multiple Myeloma, Gallbladder, Pancreatic, Gastrointestinal Tract, Small Cell Lung Cancer, Bladder, Head & Neck, and Sarcoma.