Girisopam (GYKI 51189), a 2,3-benzodiazepine, is a compound with anxiolytic and antipsychotic action. It has shown these effects in several animal models. Girisopam differs from the traditional 1,4-benzodiazepines because of its selective anxiolytic action without muscle relaxant and anticonvulsive activity, and because it does not have affinity for 1,4-benzodiazepine receptors. Antidepressant activity of girisopam was also reported. The binding site of girisopam in neuronal cells in the central nervous system is located exclusively to the basal ganglia. Because the danger of tolerance and dependence is lower for 2,3-benzodiazepine than 1,4-benzodiazepines, girisopam may potentially be used in treatment of addiction and affective disorders. No clinical trials were conducted in the US.

Rilmakalim (HOE-234) is a potassium channel activator and dilator of bronchial and vascular smooth muscles. An animal study showed that rilmakalim is effective against contractile response induced by asthma mediators in guinea pig airways and has the potential to act against asthma attacks, because it acts on acute bronchospasm. The activation of ATP-sensitive potassium channels is likely to be involved in the smooth muscle relaxation produced by rilmakalim in human airways. This drug has been investigated for use in asthma and coronary disorders, but development has been discontinued.

Naluzotan (PRX-00023), a small molecule, non-azapirone, dual serotonin (5-HT)1A receptor agonist and sigma-1 receptor antagonist, is under development with Proximagen for the treatment of epilepsy. In previous clinical trials, the compound was shown to be safe and well-tolerated in over 400 patients. Epilepsy patients with localisation-related epilepsy have reduced 5-HT1a receptor binding as indicated by positron emission tomography (PET scan). It is thought that by increasing neurotransmitter activity at 5-HT1a receptor sites, seizure incidence and severity may be decreased.

Flutroline, an antipsychotic drug that was studied to treat patients with schizophrenia. Clinical trials have shown that the drug was a safe, effective, and 20 mg and above offered the best potential for optimal clinical effectiveness. However, information about the further development of this drug is not available.

Ezutromid (SMTC-1100) is a small molecule utrophin upregulator. Ezutromid was identified from an iterative analoging approach from initial hits identified using a human muscle-specific utrophin A promoter cell-based assay. It increases both utrophin RNA and protein resulting in a significant reduction in dystrophic symptoms and increased muscle function in dystrophin-deficient mdx mice ( a mouse model of Duchenne muscular dystrophy (DMD)). Ezutromid was deemed safe and well tolerated in a Phase 1a healthy volunteer study and successfully completed a Phase 1b study in DMD boys. Summit Therapeutics is developing Ezutromid for the treatment of Duchenne muscular dystrophy.

Semotiadil (also known as sesamodil or SD 3211) is a (+)-(R)-stereoisomer, the corresponding (−)-(S)-stereoisomer is called levosemotiadil. Semotiadil, a benzothiazine derivative was developed as a novel Ca2+ channel blocker with antiplatelet activity. Experiments on rodents have revealed that the drug had an advantage in the treatment of angina with regard to long-lasting action and selectivity for coronary artery and myocardium. In addition, semotiadil improved survival of rats with monocrotaline-induced pulmonary hypertension: comparison with diltiazem. Semotiadil was studied in phase II clinical trials for the treatment of angina pectoris and hypertension in Europe, and in Japan for the treatment of arrhythmias. However, the further development of semotiadil has now been discontinued.

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.

Epelsiban (GSK557296), a pyridyl-2,5-diketopiperazine, is a potent, highly selective, and orally bioavailable non-peptide oxytocin receptor antagonist. GlaxoSmithKline was developing epelsiban for the treatment of women infertility due to adenomyosis and premature ejaculation.

Indocate is indole derivative and monoamine oxidase inhibitor with peripheral antiserotonin properties.

Refametinib (RDEA-119, BAY- 869766) is a highly potent and selective inhibitor of mitogen-activated ERK kinase (MEK1/2) activity, Refametinib binds to an allosteric pocket adjacent to the ATP binding site, locking the enzyme in a catalytically inactive conformation. This compound is highly efficacious at inhibiting cell proliferation in several tumor cell lines in vitro. In vivo, Refametinib exhibits potent activity in xenograft models of cancers. Ardea Biosciences (a subsidiary of AstraZeneca) and Bayer HealthCare are developing refametinib for the treatment of cancer. The sulfonamide agent was originally developed by Valeant Pharmaceuticals International. Refametinib is in phase II development for hepatocellular carcinoma, and phase I/II development for pancreatic cancer and other solid tumours.