Dimethyl fumarate (DMF) is the methyl ester of fumaric acid. DMF was initially recognized as a very effective hypoxic cell radiosensitizer. Later, DMF combined with three other fumaric acid esters (FAE) was licensed in Germany as oral therapy for psoriasis (trade name Fumaderm). Phase III clinical trials found that DMF (BG-12) successfully reduced relapse rate and increased time to progression of disability in multiple sclerosis (trade name Tecfidera). DMF is thought to have immunomodulatory properties without significant immunosuppression. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.

Levomilnacipran (1S, 2R/F2695) is an enantiomer of milnacipran, a serotonin/norepinephrine (5-HT/NE) reuptake inhibitor. Levomilnacipran is pharmacologically more active as compared with racemic mixture and dextromilnacipran (1R, 2S/F2696). The safety of the drug is also higher than the safety of a racemate, resulting in a beneficial impact on the therapeutic effect. Pierre Fabre and Forest Laboratories are developing levomilnacipran extended release (ER) [FETZIMA™], an enantiomer of milnacipran, for the treatment of major depressive disorder (MDD). In addition, Pierre Fabre (the originator of the compound) is developing the drug to improve recovery in patients with ischaemic stroke.

Apocynin, also known as acetovanillone, is a natural organic compound related to vanillin. It has been isolated from a variety of plant sources. Metabolites of apocynin are able to block the activity of NADPH oxidase, thus giving apocynin antioxidant and anti-inflammatory capabilities. Effects of apocynin on the concentration of reactive oxygen and nitrogen species in patients with asthma and chronic obstructive pulmonary disease were investigated in phase I clinical trials. In preclinical models, it was found that apocynin provides neuroprotective effects in models of stroke and Parkinson's disease.

Cutamesine, an agonsit of brain sigma 1 receptors, was developed by Santen Pharmaceutical for the treatment of cognitive diseases. The drug was tested in phase II in patients with major depressive disorders and for recovery of patients with stroke, however its development was terminated for the given conditions. Currently M's science corporation is developing cutamesine for Amyotrophic lateral sclerosis and Retinitis pigmentosa as more suitable target diseases.

SITOGLUSIDE (Daucosterol) inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner. It also perturbs cell cycle and induces apoptotic cell death in A549 cells. Daucosterol has being shown to promote the proliferation of neural stem cells. Daucosterol also protects neurons against oxygen-glucose deprivation/reperfusion-mediated injury by activating IGF1 signaling pathway. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.

Solasodine is an aglycone of solamargine and solasonine, which are the major solasodine glycosides present in numerous species of the solanaceae family including potato, tomato or garden egg plant etc. In Phase II clinical trial was shown that solasodine glycosides exhibit anticancer activity against skin cancer. The effects of aglycone solasodine on cancer cells have also been investigated. Solasodine inhibits the growth of human colon and liver cancer cell. In addition, solasodine effectively inhibits proliferation of HER2-overexpressing breast cancer cells and inhibits invasion of human lung cancer cells. Solasodine possesses CNS activities such as antipyretic, anticonvulsant and memory enhancing effects. Also, solasodine has been found to possess diuretic, antifungal, hepatoprotective, immunomodulatory, anti-spermatogenetic and antiandrogenic effects.

Schisantherin A is a dibenzocyclooctadiene originally found in Schisandra that exhibits anti-tussive, sedative, anti-inflammatory, anti-osteoporotic, neuroprotective, cognition enhancing, and cardioprotective activities. In macrophages, schisantherin A decreases LPS-induced expression and activity of iNOS, COX-2, NO, IL-6, and TNF-α. Schisantherin A also decreases RANKL-induced NF-κB signaling by inhibiting IκBα degradation and suppressing JNK and ERK1/2 activation in vitro; it also inhibits osteoclast function and bone erosion in vivo. In animal models of Alzheimer’s disease, schisantherin A inhibits amyloid-β (Aβ)-induced learning and memory impairments in Y maze, shuttle box, and Morris water maze assays. Additionally, this compound lowers left ventricular systolic and end diastolic pressures, decreases infarct size and maldionaldehyde release, and increases superoxide dismutase activity, preventing myocardial apoptosis in animal models of cardiac ischemia/reperfusion. Schisantherin A conferred significant protection against MPTP-induced loss of TH-positive dopaminergic neurons in a Parkinson's disease (PD) mice model. Western blotting analysis demonstrated that Schisantherin A exhibited neuroprotection against MPP(+) through the regulation of two distinct pathways including increasing CREB-mediated Bcl-2 expression and activating PI3K/Akt survival signaling suggesting that StA might be a promising neuroprotective agent for the prevention of PD.

Piceatannol (3,3′,4,5′-tetrahydroxy-trans-stilbene; PIC) is a naturally occurring stilbene present in diverse plant sources. Piceatannol is a hydroxylated analog of resveratrol and produced from resveratrol by microsomal cytochrome P450 1A11/2 and 1B1 activities. Like resveratrol, Piceatannol has a broad spectrum of health beneficial effects, many of which are attributable to its antioxidative and anti-inflammatory activities. Piceatannol exerts anticarcinogenic effects by targeting specific proteins involved in regulating cancer cell proliferation, survival/death, invasion, metastasis, angiogenesis, etc. in the tumor microenvironment. Piceatannol also has other health promoting and disease preventing functions, such as anti-obese, antidiabetic, neuroprotective, cardioprotective, anti-allergic, anti-aging properties. A comprehensive review of PIC concludes that the compound has the health promoting and disease preventive potential. However, low water-solubility and bioavailability of PIC limit its pharmaceutical application and also use in functional foods. In this context, it is noticeable that beta-cyclodextrin was found to improve the bioavailability, the solubility and the stability of Piceatannol.

Selfotel is a competitive NMDA antagonist with (-)-enantiomer is more active than ( )-enantiomer. Selfotel was investigated in phase III clinical trials for ischemic stroke and severe head injury. Development of the drug was discontinued due to lack of efficacy and possible neurotoxicity discovered in clinical trials.

Acetyltryptophan, L- functions readily as a component of the food in place of the free amino acid. Acetyltryptophan, L- is a neurokinin-1 receptor antagonist. It significantly improved motor and cognitive outcomes in models of Parkinson’s diseases, as well as reduced brain edema and axonal injury in experimental traumatic brain injury and stroke. It is a potent therapeutic agent for the treatment of amyotrophic lateral sclerosis.