Nicaraven is a hydroxyl radical scavenger with antivasospastic and neuroprotective effects. Chugai (the Japanese subsidiary of Roche) is developing nicaraven (Antevas), a water-soluble antioxidant, for the potential treatment of disorders caused by acute cerebrovascular diseases. A registration application was filed in April 1995, and in April 2002, nicaraven was still awaiting registration in Japan. By August 2002, Chugai had filed an NDA in Japan for the additional indication of subarachnoidal bleeding.

Evenamide (NW-3509) is a blocker of voltage-gated sodium channels. Evenamide modulates sustained repetitive firing, without inducing impairment of normal neuronal excitability. It normalizes glutamate release induced by aberrant sodium channel activity. The potential benefits of the compound have been demonstrated in numerous preclinical models predictive of efficacy in psychiatric diseases, including models of psychosis such as amphetamine-induced hyperactivity, sensorimotor gating and information processing deficits (pre-pulse inhibition impairment induced by different stimuli), mania and depression. Evenamide is being evaluated in a Phase II trial as add-on treatment to 5HT2/D2 blocking antipsychotics in schizophrenic patients.

Cyproximide is a psychoactive drug discovered by American Cyanamid company. The drug exhibited activity as a central nervous system depressant and was claimed to be useful as a tranquilizing agent, hypnotic agent or muscle relaxant. The phenobarbital-like activity of cyproximide after intraperitoneal administration was demonstrated in rod traversal, clinging and righting reflex tests in mice. In addition to CNS depressant activity, cyproximide had a mild stimulant and antidepressant effects, which were shown by the restoration of exploratory behavior and an increase in locomotor activity in mice. Chronic administration of the drug led to a greater incidence of proliferative lesions in the liver of treated rats; however, the incidence of hepatocellular neoplasms was the same in treated and control rats.

Amibegron (SR 58611A or SR 58611) is a highly selective agonist for atypical beta3-adrenoceptors. It stimulates neuronal activity in a specific area of the prefrontal cortex and also inhibits intestinal motility. Amibegron was in phase III trials worldwide for the treatment of depression and generalised anxiety disorder but development of the product was discontinued in 2008. Amibegron has been tested for its potential as a treatment for irritable bowel syndrome.

Neboglamine is a functional modulator of the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Neboglamine appeared to promote neuronal growth as measured by expression of Fos-like immunoreactivity, particularly in the prefrontal cortex, nucleus accumbens, and lateral septal nucleus. Neboglamine behaves as a potential antipsychotic. Neboglamine is in phase II clinical trials by Rottapharm for the treatment of schizophrenia and cocaine abuse.

Eterobarb (Antilon) is a barbiturate derivative. It is an effective anticonvulsant as demonstrated in animal and clinical studies. Eterobarb possesses a unique and clinically intriguing feature-at therapeutically effective blood levels, the hypnotic side effects usually associated with barbiturates appear absent. Though effective against both electrically and chemically induced seizures in mice and rats, virtually no hypnotic effects were noted except at lethal doses. Double-blind cross-over studies have confirmed the anticonvulsant efficacy of eterobarb and several phase II and phase Ill studies show eterobarb to be an effective anticonvulsant with less hypnotic activity when compared with phenobarbital. Eterobarb had been NDA filed for the treatment of epilepsy in the US, UK, Switzerland and Canada. However, this research has been discontinued. The compound was originated by Colgate Palmolive, then licensed to MacroChem.

Esuprone (LU 43839) is a monoamine oxidase type A inhibitor. Esuprone proved to be an effective anticonvulsant in the kindling model. Esuprone was undergoing phase II clinical trials with Knoll (BASF Pharma) in Germany as an antidepressant.

Dicarbine is an orally active drug approved in Russia under the trade name Карбидин, is used for the treatment patients with schizophrenia and alcoholic psychosis. This drug blocks dopamine receptors in various brain parts, which leads to a reduction in the productive symptoms of psychosis: delusions and hallucinations.

Tarenflurbil (Flurizan or R-flurbiprofen) is the single enantiomer of the racemate NSAID flurbiprofen. Tarenflurbil is a first in class, selective amyloid-beta42 (A42) lowering agent (SALA), which acts by modulating the activity of gamma-secretase, an enzyme that converts amyloid precursor protein to amyloid-beta. The reduction of A42 may prevent the development of the amyloid plaques thought to be a key pathological process associated with Alzheimer’s disease. For several years, research and trials for the drug were conducted by Myriad Genetics, to investigate its potential as a treatment for Alzheimer's disease. In a brief statement issued June 30, Myriad Genetics reports that tarenflurbil (Flurizan) failed to have a significant effect in a phase 3 trial of patients with mild Alzheimer's disease (AD). The failure of Flurizan™ is generally attributed to its insufficient pharmacodynamics, i.e., inadequate ability to penetrate the brain and engage its target protein at doses sufficient to yield an effect. Two additional Phase 3 trials were terminated and further development of Flurizan™ was discontinued. Separate clinical development of Flurizan™ for prostate cancer has also been discontinued following negative Phase 2 results. Tarenflurbil activates c-Jun N terminal kinase, increases AP-1 binding to DNA, and downregulates cyclin D1 expression, resulting in the arrest of tumour cells in the G1 phase of the cell cycle and apoptosis. This agent also affects the expression of nuclear factor kappa B, a rapid response transcription factor that stimulates the immune response to tumour cells. Tarenflurbil does not inhibit the enzyme cyclooxygenase. The Fraunhofer Institute for Molecular Biology and Applied Ecology is currently developing tarenflurbil for the treatment of relapsing, remitting multiple sclerosis.

Sulazepam is a desmethylbenzodiazepine. It is the thioamide derivative of diazepam. It has sedative, muscle relaxant, hypnotic, anticonvulsant and anxiolytic properties like those of other benzodiazepines. Sulazepam in vivo in experimental animals undergoes enzymic desulfonation, demethylation, and [3C] hydroxylation, with the formation of basic metabolites: diazepam, desmethyldiazepam, and oxazepam.