Nefiracetam is a cyclic derivative of gamma-aminobutyric acid (GABA). It is thought to act by normalising dysfunctional acetylcholine, GABA and possibly monoamine neurotransmitter systems, but it may also facilitate N/L-type calcium channel opening. Nefiracetam has received attention as a treatment for seizures, depression, and dementia. Nefiracetam was found to be extremely testicular toxic in both rats and dogs; it was found to significantly decrease the levels of testicular testosterone leading to atrophy and malformation of sperm.

Seletracetam, a pyrrolidone derivative is a new drug in epilepsy development. Seletracetam has high binding affinity to the synaptic vesicle 2A (SV2A) protein. In addition, was discovered, that the drug bound to N-type calcium channels and inhibited high-voltage-activated Ca2+ currents and intracellular Ca2+ increase. Seletracetam participated in Phase III clinical trials; however, all these studies for the treatment of epilepsy were terminated. Moreover, it is unknown whether planned phase IIb/III trials will begin.

Ebalzotan is a selective serotonin (5-HT1A) receptor agonist, was chosen by Astra in the early 1990s as a candidate drug for the treatment of depression and anxiety. It has a modest affinity for the 5-HT(7). In vivo, ebalzotan induced all the typical effects of a 5-HT(1A) receptor agonist in rats: it decreased 5-HT synthesis (5-HTP accumulation) and 5-HT turnover (measured as the ratio of 5-hydroxyindoleacetic acid/5-HT), increased corticosterone secretion, induced the 5-HT(1A) syndrome (flat body posture and forepaw treading), inhibited the cage-leaving response, and caused hypothermia. Ebalzotan had been in phase I clinical trial for the treatment of major depressive disorder. However, this study was discontinued.

Dimesna is a prodrug of mesna (dimer of mesna). Dimesna is reduced to mesna in the kidneys. Dimesna does not prevent cellular damage by metabolites of ifosfamide and cyclophosphamide in the renal tubular cell line LLC-PK1. Dimesna is a mucolytic agent used to alleviate toxic side effects of antitumor drugs. The organic acid transporter OAT4 on the luminal side of the proximal renal tubule facilitates the reabsorption of dimesna, and therefore its reduction to mesna, whereas the multidrug and toxin extrusion protein MATE1, the multidrug resistance protein MRP2, and P glycoprotein facilitate the efflux of mesna and/or dimesna back into the lumen; dimesna may also be excreted unchanged by MRP4. It has therefore been suggested that polymorphism of these renal transport proteins or transporter-mediated drug-drug interactions may reduce the efficacy of mesna and dimesna.

Oxfenicine is a CPT-1b-specific inhibitor. It must be transaminated to its active form, 4-hydroxyphenyl-glyoxylate, which is competitive with carnitine, preventing the formation of acylcarnitine. Because CPT-1b shows the highest sensitivity to 4-hydroxyphenyl-glyoxylate, inhibition of fatty acid oxidation by oxfenicine takes place selectively in those tissues that express this CPT isoform. It may be effective for treating noninsulin-dependent diabetes mellitus which is characterized by elevated fatty acid levels and obesity. In 1980 it was also tested in preclinical models of angina pectoris and ischemia.

Halofenate (MK-185) was invented as a hypolipidemic and hypouricemic agent. It was shown that halofenate lower serum triglycerides and uric acid in patients with a variety of hyperlipidemias. Treatment of dyslipidemic type 2 diabetic patients also showed triglyceride lowering and, surprisingly, significant reductions in plasma glucose and insulin. Halofenate is a selective PPAR-γ modulator (SPPARγM). SPPARγMs are believed to bind in distinct manners to the ligand-binding pocket of PPAR-γ, leading to altered receptor conformational stability and resulting in distinct patterns of gene expression. Thus, was suggested that halofenate hold promising therapeutic potential in the treatment of type 2 diabetes, without the side effects. However, information about the current use of this compound is not available.

S-Allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract, has multifunctional activity via different mechanisms and neuroprotective effects that are exerted probably via its antioxidant or free radical scavenger action. Anticancer effects of SAC were reported in prostate cancer, breast cancer, oral cavity cancer, non-small cell lung cancer, neuroblastoma, and hepatocellular carcinoma through the restoration of E-cadherin, the reduction of Slug and matrix metalloproteinase (MMP) protein expression, and stimulating apoptotic pathways. In addition, recently was revealed, that SAC might have imperative implications for the deterrence and early treatment of type 2 diabetes by reducing the influx of glucose in the polyol pathway, thereby elevating the GSH level and reducing the activities of aldose reductase (AR) and sorbitol dehydrogenase (SDH).