Siramesine is a sigma2 opioid agonist under development by H Lundbeck as a potential treatment for anxiety. In March 1998, the compound was licensed to Forest Laboratories under a strategic alliance. In August 2000, siramesine entered phase II trials. Siramesine has been shown to trigger cell death of cancer cells and to exhibit a potent anticancer activity in vivo. Siramesine triggers cell death through destabilisation of mitochondria, but not lysosomes. Siramesine is a lysosomotropic detergent that induces cytoprotective autophagosome accumulation. Siramesine involves lysosomal leakage and oxidative stress.

Fenaperone exerts tranquilizing and neuroleptic properties.

Carburazepam (also known as Uxepam) is benzodiazepine derivative with potent anxiolytic activity and slight muscle relaxant effect. Carburazepam suppresses the avoidance reflex, orienting-research behavior and motor activity, disturbs movement coordination in rats.

Iclazepam (also known as Clazepam) was used as a tranquilliser.

Perafensine is an isoquinoline derivative shown to be active in tests predictive of antidepressant activity. Perafensine is a potent antagonist of reserpine-induced effects and inhibits norepinephrine uptake into rat hypothalamic synaptosomes. Perafensine induced the biosynthesis of microsomal drug-metabolizing enzymes – in treated rats methylayapanine O-demethylase, ethoxycoumarin O-deethylase and cytochrome P-450 contents were increased and ketamine N-demethylase was decreased.

Pexacerfont is a highly potent and selective CRF1 receptor antagonist that displays no agonist properties. It is specific for CRF1 receptors and has more than 1,000- fold less affinity for CRF2 receptors, and more than 100- fold less affinity for the CRF-binding protein. In extensive preclinical studies, pexacerfont has been shown to inhibit specific binding of CRF to rat, dog, monkey, and human CRF1 receptors. The functional anxiolytic effects of CRF1 receptor occupancy were demonstrated in two rodent models of anxiety, situational anxiety and elevated plus maze paradigms. Pexacerfont did not demonstrate efficacy compared to placebo for the treatment of generalized anxiety disorder in human. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor. Pexacerfont had been in phase II clinical trials for the treatment of irritable bowel syndrome and depression depression.

Imagabalin is a ligand to the α(2)δ subunit of voltage-sensitive calcium channel and was developed to treat generalized anxiety disorder. Imagabalin was involved in phase III clinical trials when was made a decision to terminate all studies. However, this decision was not based on any safety concerns.

Climazolam is a benzodiazepine derivative, developed by Hoffman-LaRoche. It was used in veterinary for anesthetizing animals.

Nerisopam [EGIS 6775, GYKI 52322] is a novel 2,3-benzodiazepine derivative with both anxiolytic and antipsychotic activity in animal studies. Nerisopam induces rapid, intense expression of Fos-like immunoreactivity in the rostral, dorsomedial and lateral parts of the striatum in the rat. The striatal neurons are the primary targets of this anxiolytic and antipsychotic drug in the central nervous system. Nerisopam does not bind to the central dopamine receptors, but it shows affinity to the 5-HT1 receptors (IC50 = 7.1 x 10(-6) mol/l) and inhibits brain cAMP-phosphodiesterase (IC50 = 2.4 x 10(-5) mol/l). Nerisopam development for the treatment of anxiety disorder and schizophrenia were discontinued in phase 1.

Paraxazone is a monoamine oxidase Inhibitor that was studied as an antidepressant but has never been marketed. Information about the current use of this drug is not available.