Deptropine citrate is a well-known H1-histamine receptor antagonist and muscarinic receptor antagonist. It is prescribed frequently for treatment of asthma, although there has been a sharp decrease in prescriptions since 1994. Deptropine is gradually being replaced by inhaled beta 2 adrenergic agonists and glucocorticosteroids as the preferred clinical prescription. Recently deptropine has garnered interest as a potential treatment for breast cancer. In vitro studies have shown deptropine citrate has inhibitory effects on cell viability and mammosphere formation in Breast Cancer Stem Cells (BCSCs). However, it does not seem to inhibit the self-renewal capacity of the breast cancer cell line MDA-MB-231 when it is enriched with Cancer Stem Cells.

Watanidipine (AE0047) had been NDA filed for the treatment of hypertension in Japan. Watanidipine (as Calbren®) was awaiting registration with Mitsubishi Pharma Corporation in Japan. However, Mitsubishi Pharma Corporation has discontinued the development of this drug. Watanidipine had also been in phase II clinical trials for the treatment of stroke and preclinical trials for atherosclerosis. However, no recent development has been reported. Watanidipine (AE0047) has being shown to be a calcium antagonist with protective effects against cerebral ischaemia and the occurrence of stroke in several animal models.

Oxitropium bromide (trade names Oxivent, Tersigan) is a bronchodilator indicated for asthma and chronic obstructive pulmonary disease. Oxitropium’s bronchodilation effect is similar to that of ipratropium bromide, but oxitropium is longer-lasting. The usual dose is 200 ug, 2–3 times daily. It blocks the muscarinic cholinergic receptors which mediate smooth muscle contraction in the airways. The manufacturer claims that regular use of oxitropium (200μg twice or three times daily) reduces the incidence of symptoms, including the need for night-time bronchodilators, and improves lung function in some patients; it is not intended for immediate symptom relief. Although widely used for many years (alone or in combination with short-acting beta agonists) for both maintenance treatment of stable disease and exacerbation of airway obstruction, Boehringer Ingelheim announced the discontinuation of Oxivent formulations at May 2004.

Bupranolol is a non-selective beta blocker without intrinsic sympathomimetic activity (ISA), but with strong membrane stabilizing activity. Bupranolol competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart, inhibiting sympathetic stimulation. This results in a reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension. Ophthalmic Bupranolol is used for the management of glaucoma and oral Bupranolol is used for the management of cardiovascular disorders. S-Bupranolol has also being shown to have superior preclinical safety profile and great antinociceptive efficacy and should be considered as a unique b-AR compound to advance future clinical pain studies.

Mepitiostane is a epitiostanol prodrug that was developed in Japan by Shionogi. The drug is approved and used exclusively in Japan for the treatment of breast carcinoma and anemia associated with renal failure. Upon administration mepitiostane is metabolized to the active metabolite which binds to and inhibits estrogen receptors.

Iproheptine (Metron, Susat) is a vasoconstrictor, antihistamine, nasal decongestant marketed in Japan.

Israpafant (also known as Y-24180) is a drug which acts as a selective antagonist for the platelet-activating factor receptor, and was originally developed for the treatment of asthma. Its chemical structure is a thienotriazolodiazepines, closely related to the sedative benzodiazepine derivative etizolam. However, israpafant binds far more tightly to the platelet-activating factor receptor, with an IC50 of 0.84nM for inhibiting PAF-induced human platelet aggregation, while it binds only weakly to benzodiazepine receptors, with a Ki of 3680nM. Israpafant has been found to inhibit the activation of eosinophil cells and consequently delays the development of immune responses. It has also been shown to have anti-nephrotoxic properties and to mobilize calcium transport.

Fabesetron is a dual 5HT3 and 5HT4 receptors antagonist that was developed in Japan for the treatment of chemotherapy-induced emesis and gastrointestinal disorders. The development of the drug was terminated in phase II.

Azasetron is an antiemetic drug. It acts as serotonin 3 receptor antagonist. It is currently used to prevent nausea and vomiting caused by cancer chemotherapy (including cisplatin chemotherapy). Also it was demonstrated that azasetron has potent antimitogenic and apoptotic effect on cancer cell line. It was preclinically tested to treat cocaine abuse.

Methylnaltrexone bromide, (17s)- (methylnaltrexone bromide), a quaternary amine of the pure narcotic antagonist naltrexone, is a peripherally-acting selective mu-opioid antagonist. Methylnaltrexone antagonizes opioid binding at mu-opioid receptors, half-maximal inhibitory concentration (IC50) of 70 nM. It has a relatively lower affinity for κ-opioid receptors (IC50 575 nM), and it does not interact with δ-receptors or orphanin FQ receptors. Approved by FDA in the United States under the trade name Relistor, methylnaltrexone bromide is indicated for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when the response to laxative therapy has not been sufficient. Restricted ability to cross the blood-brain barrier allows methylnaltrexone bromide to function in tissues such as the gastrointestinal tract, decreasing the constipating effects of opioids without impacting opioid-mediated analgesic effects on the central nervous system.