Bakuchiol is a prenylated phenolic monoterpene isolated from Psoralea corylifolia Leguminosae, widely used in Chinese and Indian traditional medicine for the treatment of premature ejaculation, knee pain, alopecia spermatorrhea, enuresis, backache, pollakiuria, vitiligo, callus, and psoriasis. Bakuchiol is shown to have anti-microbial, anti-inflammatory, anti-oxidative, anti-osteoporosis, and anti-depression or anti-stress activities The anti-cancer potential of bakuchiol has been. Bakuchiol inhibits liver cancer cell growth through inducing S phase arrest, caspase 9/3 activation, p53 and Bax up-regulation, as well as Bcl-2 down-regulation. It also inhibits human carboxylesterase 2, which is commonly expressed in tumor tissue and involved in the metabolism of endogenous lipids and drugs.

Domperidone is a peripherally selective D2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine. Domperidone was not approved in USA due to risks of cardiac arrhythmias, cardiac arrest, and sudden death, but is available in other countries. However, FDA allows access to Domperidone through an expanded access investigational new drug application (IND) to patients with gastroesophageal reflux disease with upper GI symptoms, gastroparesis, and chronic constipation. As an “off-label” use, domperidone is prescribed to breastfeeding women to enhance their milk production.

3-N-Butylphthalide (NBP), a family comprised of optical isomers l-3-N-butylphthalide (l-NBP) and d-3-N-butylphthalide (d-NBP), with l-NBP being an extract from seeds of Apium graveolens Linn. (celery) and dl-3-N-butylphthalide (dl-NBP), a synthetized version, has been studied for its significant neuroprotective effects. NBP showed neuroprotective effects by decreasing oxidative damage, inhibiting inflammatory responses, improving mitochondrial function, and reducing neuronal apoptosis. NBP received approval by the State Food and Drug Administration of China for clinical use in stroke patients in 2002. It demonstrates a potential for the treatment of central nervous system diseases, including Parkinson’s disease, Alzheimer’s disease.

Valpromide (2-propylpentanamide) is a derivative of valproic acid. Bio-pharmacological data show several possible mechanisms of action involving an increase in GABA levels in brain as well as changes in membrane conductance on neurons. Valpromide has been shown to decrease aggressivity in stress-induced animals, to regulate anxious induced behaviours, as well as to potentiate central sedative compounds. It produces a significant increase of cognitive functions. Psychopathological experiments have shown: a wakening of personality, euphoric effects, an improvement of social behaviour, a stabilization of mood in affective disorders. Valpromide is indicated for the treatment of bipolar disorder (manic episodes). It is marketed in some Europe countries.

Atreleuton is a potent, orally administered, selective 5-Lipoxygenase inhibitor. Atreleuton had been in phase III clinical trials for the treatment of asthma and phase II clinical trials for the treatment of acute coronary syndrome and atherosclerosis. However, this research has been discontinued.

Tofisopam (marketed under brand names Emandaxin and Grandaxin) is a 2,3-benzodiazepine derivative that is marketed in several European countries as the anxiolytic drug. Tofisopam does not bind to the benzodiazepine binding site of the gamma-aminobutyric acid receptor. One study has shown that tofisopam acts as an isoenzyme-selective inhibitor of phosphodiesterases (PDEs) with the highest affinity to PDE-4A1 followed by PDE-10A1, PDE-3, and PDE-2A3. Like other benzodiazepines, tofisopam possesses anxiolytic properties but unlike other benzodiazepines, it does not have anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing or amnestic properties. While it may not be an anticonvulsant in and of itself, it has been shown to enhance the anticonvulsant action of classical 1,4-benzodiazepines such as diazepam (but not sodium valproate, carbamazepine, phenobarbital, or phenytoin). Tofisopam is not approved for sale in the United States or Canada. However, Vela Pharmaceuticals of New Jersey is developing the D-enantiomer (dextofisopam) as a treatment for irritable bowel syndrome, with moderate efficacy demonstrated in clinical trials so far.

Evocalcet (MT-4580, KHK7580) is an allosteric calcium-sensing receptor agonist. Evocalcet directly acts on calcium receptors on parathyroid cells to suppress synthesis and secretion of parathyroid hormone (PTH), and it consequently decreases serum PTH and serum calcium. ORKEDIA® TABLETS (generic name: evocalcet, code name: KHK7580) has been listed on the National Health Insurance (NHI) Drug Price List and launched for the treatment of secondary hyperparathyroidism in patients on maintenance dialysis in Japan.

Ripasudil (K-115) is a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor. This compound, which was originally discovered by D. Western Therapeutics Institute, Inc., reduces intraocular pressure (IOP) by directly acting on the trabecular meshwork, thereby increasing conventional outflow through the Schlemm's canal. As a result of this mechanism of action, ripasudil may offer additive effects in the treatment of glaucoma and ocular hypertension when used in combination with agents such as prostaglandin analogues (which increase uveoscleral outflow) and β blockers (which reduce aqueous production). GLANATEC® (Ripasudil hydrochloride hydrate) ophthalmic solution 0.4% is launched in Japan for the treatment of glaucoma and ocular hypertension.

Naphthoquine is an antimalarial drug first synthesized in China in 1986 but which was not developed for clinical use until the late 1990s. This drug now is used in combination for treatment of Plasmodium Falciparum and Malaria. The use of anti-malarial drug combinations with artemisinin or with one of its derivatives is now widely recommended to overcome drug resistance in falciparum as well as vivax malaria. The fixed oral dose artemisinin-naphthoquine combination (ANQ, ARCO™) is a newer artemisinin-based combination (ACT) therapy undergoing clinical assessment.

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.