Linopirdine [DuP 996, 3, 3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one], a putative cognition enhancing drug, increases acetylcholine release in rat brain tissue and improves performance in animal models of learning and memory. Linopirdine was developed as a cognitive enhancing molecule and demonstrated to specifically block the potassium current generated by the brain specific KCNQ2-KCNQ3 proteins (M-channel). Linopirdine also acts as an agonist of TRPV1. At low concentrations linopirdine sensitizes both recombinant and native TRPV1 channels to heat, in a manner that is not prevented by the Kv7-channel opener flupirtine. Taken together, these results indicate that linopirdine exerts an excitatory action on mammalian nociceptors not only through inhibition of the M current but also through activation of the capsaicin receptor TRPV1. In the late 1980s, DuPont initiated clinical trials with linopirdine for Alzheimer’s disease. Linopirdine was regarded as a promising drug because it enhanced the release of acetylcholine in cholinergic nerve terminals in the brain only when its release was triggered and improved learning and memory in rodents and primates. Although clinical trials with linopirdine remained largely inconclusive or showed that it did not improve memory performance in elderly subjects, linopirdine became a valuable pharmacological tool. Development of Linopirdine for the treatment of Alzheimer's disease was discontinued.

Laquinimod is a new orally available carboxamide derivative, which is currently developed for relapsing remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative diseases. The mechanism of action of laquinimod is not fully elucidated because the molecular target is not known. Treatment with laquinimod led to a significant and persistent increase in brain-derived neuroprotective factor (BDNF) serum levels compared to placebo treatment. In human studies, a decrease of pro-inflammatory and an increase of anti-inflammatory cytokines have been measured. After commercial launch the unexpected severe cardiac adverse events (AEs) such as serositis, pericarditis, and myocardial infarction were detected.

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.

Floctafenine is an analgesic agent used for the treatment of pain. The drug exerts its anti-inflammatory action by inhibiting COX-1 and COX-2, with a slight preference towards COX-1. Floctafenine is marketed in Canada under the name Floctafenine and it is withdrawn in Europe (Idarac Brand name).

Carisbamate is an experimental anticonvulsant drug that was under development by Johnson & Johnson Pharmaceutical Research and Development but never marketed. Acute and chronic nonclinical toxicological studies have not revealed any significant abnormalities other than dose-related CNS toxicity. Carisbamate displays high potency in a broad range of rodent seizure and epilepsy models at doses well below those that produce CNS toxicity. The exact mechanism of action is unknown but neuroprotective and antiseizure activity of Carisbamate likely results in part from decreased calcium accumulation through blockade of T-type Ca2+ channels. A phase II clinical trial in the treatment of partial seizures demonstrated that the compound has efficacy in the treatment of partial seizures and a good safety profile. In large multicenter phase III clinical trial for the treatment of partial seizures carisbamate at doses of 300, 800, and 1,600 mg/d was effective as adjunctive therapy for reducing the frequency of partial-onset seizures. The most common adverse events, encountered mainly at daily doses of 1000 mg or more, were CNS-related, including headache, dizziness, somnolence, and nausea. In another phase III clinical trial, carisbamate was not more efficacious in migraine prophylaxis than placebo, but carisbamate monotherapy was well tolerated at doses up to 600 mg per day. Johnson & Johnson received provisional approval by the FDA to market carisbamate under the brand name of Comfyde. However, on August 21, 2009, Johnson & Johnson reported that the FDA had failed to give marketing approval.

Bentazepam (also known as Thiadipone, Tiadipona) is a benzodiazepine analog, used as a short-action anxiolytic. Bentazepam a thienodiazepine with the same main mechanism of action as the classic 1,4-benzodiazepines, is a short-action anxiolytic, with an elimination-half-life of 3 to 5 hours in healthy volunteers. Bentazepam possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. A severe benzodiazepine overdose with bentazepam may result in coma and respiratory failure. Adverse effects include dry mouth, somnolence, asthenia, dyspepsia, constipation, nausea and drug-induced lymphocytic colitis has been associated with bentazepam. Severe liver damage and hepatitis has also been associated with bentazepam. Whilst liver failure from bentazepam is considered to be rare, liver function monitoring has been recommended for all patients taking bentazepam.

Tiapride is a drug that selectively blocks D2 and D3 dopamine receptors in the brain. It is used to treat a variety of neurological and psychiatric disorders including dyskinesia, alcohol withdrawal syndrome, negative symptoms of psychosis, and agitation and aggression in the elderly. A derivative of benzamide, tiapride is chemically and functionally similar to other benzamide antipsychotics such as sulpiride and amisulpride known for their dopamine antagonist effects. Tiapride is marketed under various trade names and is widely available outside of the United States. The most common trade name for tiapride is Tiapridal, which is used throughout Europe, Russia, as well as parts of South America, the Middle East, and North Africa. It is also sold under different names in Italy (Italprid, Sereprile), Japan (Tialaread, Tiaryl, Tiaprim, Tiaprizal), Chile (Sereprid), Germany (Tiaprid, Tiapridex), and China (Tiapride).

Zopiclone (brand names Zimovane and Imovane) is a nonbenzodiazepine hypnotic agent used in the treatment of insomnia. The therapeutic pharmacological properties of zopiclone include hypnotic, anxiolytic, anticonvulsant, and myorelaxant properties. Zopiclone and benzodiazepines bind to different sites on GABAA-containing receptors, causing an enhancement of the actions of GABA to produce the therapeutic and adverse effects of zopiclone. The metabolite of zopiclone called desmethylzopiclone is also pharmacologically active, although it has predominately anxiolytic properties. One study found some slight selectivity for zopiclone on α1 and α5 subunits, although it is regarded as being unselective in its binding to α1, α2, α3, and α5 GABAA benzodiazepine receptor complexes. Desmethylzopiclone has been found to have partial agonist properties, unlike the parent drug zopiclone, which is a full agonist. The mechanism of action of zopiclone is similar to benzodiazepines, with similar effects on locomotor activity and on dopamine and serotonin turnover. A meta-analysis of randomised controlled clinical trials that compared benzodiazepines to zopiclone or other Z drugs such as zolpidem and zaleplon has found few clear and consistent differences between zopiclone and the benzodiazepines in sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia, and daytime alertness. After oral administration, zopiclone is rapidly absorbed, with a bioavailability around 75–80%. Time to peak plasma concentration is 1–2 hours. High-fat meal preceding zopiclone administration does not change absorption (as measured by AUC), but reduces peak plasma levels and delays its occurrence, thus may delay the onset of therapeutic effects. The pharmacokinetics of zopiclone in humans are stereoselective. After oral administration of the racemic mixture, Cmax (time to maximum plasma concentration), area under the plasma time-concentration curve (AUC) and terminal elimination half-life values are higher for the dextrorotatory enantiomers, owing to the slower total clearance and smaller volume of distribution (corrected by the bioavailability), compared with the levorotatory enantiomer. In urine, the concentrations of the dextrorotatory enantiomers of the N-dimethyl and N-oxide metabolites are higher than those of the respective antipodes. Zopiclone is sometimes used as a method of suicide. It has a similar fatality index to that of benzodiazepine drugs, apart from temazepam, which is particularly toxic in overdose.

Nordazepam (INN; marketed under brand names Nordaz, Stilny, Madar, Vegesan, and Calmday) is a 1,4-benzodiazepine derivative with amnesic, anticonvulsant, anxiolytic, muscle relaxant, and sedative properties. Nordazepam is an active metabolite of diazepam, chlordiazepoxide, clorazepate, prazepam, pinazepam, and medazepam, used primarily in the treatment of anxiety disorders. Nordazepam is a partial agonist at the GABAA receptor, which makes it less potent than other benzodiazepines, particularly in its amnesic and muscle-relaxing effects. Nordazepam’s elimination half-life is between 36 and 200 hours, with wide variation among individuals; factors such as age and gender are known to impact it. The variation of reported half-life are attributed to differences in nordazepam metabolism and that of its metabolites as nordazepam is hydroxylated to active metabolites such as oxazepam, before finally being glucuronidated and excreted in the urine. Common side effects of nordazepam include somnolence, which is more common in elderly patients and/or people on high-dose regimens. Hypotonia, which is much less common, is also associated with high doses and/or old age.

Etoperidone is an atypical antidepressant introduced in Europe in 1977. The activity of etoperidone is made mainly by its major metabolite 1-(3'-chlorophenyl)piperazine (mCPP). mCPP binds with different affinity to most of the serotonergic receptors and adrenergic receptors. This metabolite is an agonist of 5-HT2c and an antagonist of 5-HT2a. Part of etoperidone structure contributes to the activity in the α-adrenergic receptors. Etoperidone has been studied for the treatment of depression, tremors in Parkinson, extrapyramidal symptoms and male impotence. It is not certain if it was ever approved and marketed but its current status is withdrawn.