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.

Enciprazine also known as WY-48624 or, D-3112 is a GABA A receptor agonist which was in the phase III of clinical trial for the treatment of anxiety disorders. Enciprazine was well tolerated, with low levels of sedative and asthenic side effects reported. However, research was discontinued.

Tiospirone (TSP) is an atypical antipsychotic drug. Tiaspirone appeared to be a promising antipsychotic agent as it didn`t cause extrapyramidal syndromes. It has 5HT-2 antagonistic properties as well as affinity for D2, 5HT-1a, 5HT-6 and sigma receptors. Tiospirone was in phase III clinical trials for the treatment of attention hyperactivity disorder with Mead Johnson in the USA but its development appears to have been discontinued.

Cloroperone (AHR 6134) is a derivative of butyrophenone with anxiolytic properties. In animals, cloroperone causes slight CNS depression in mice, prevents the lethal effects of d-amphetamine under crowded conditions in mice, suppresses emesis in dogs. The drug was investigated in the clinic for the treatment of psychotic patients. It was shown to be effective anxiolytic at low dosages without sedation, listlessness, drowsiness or neurologic reactions. Cloroperone is a selective binder to 5-HT2 receptors (Ki 4.5 nM).

Etazolate (EHT-0202) is a selective, positive GABAA receptor modulator has completed phase II clinical trials in patients with Alzheimer's disease. It is also a selective phosphodiesterase-4 inhibitor that is specific for cAMP. Etazolate showed anxiolytic and antidepressant activity and could be useful in managing post-traumatic stress disorder.

Serazapine (CGS15040) is an anxiolytic agent. It is structurally novel 5-HT2 receptor antagonist. Preliminary preclinical findings indicated an anticonflict effect in a behavioral suppression test, and two preliminary investigations in volunteers also suggested anxiolytic potential. In the first of these studies serazapine resembled diazepam, a reference anxiolytic drug, electroencephalographically. Additionally, in a test of psychogenic stress in volunteers it reduced cardiac output.

Gepirone (brand name Travivo) is an investigational azapirone antidepressant and anxiolytic drug in development for the treatment of major depressive disorder but has yet to be marketed. Like other azapirones, it acts as a selective partial agonist of the 5-HT1A receptor. Gepirone has been under development in the U.S. in an extended release form (referred to as Gepirone ER). It has been rejected multiple times by the FDA during the drug approval process and Phase III studies evaluating its use in the treatment of MDD were prematurely terminated. These were the initial Phase III studies of gepirone ER in MDD, and the effective dose range had not been determined. In March 2016, the FDA reversed its decision and gave gepirone ER a positive review, clearing the way for the drug to finally gain market approval in the U.S. In addition to its antidepressant and anxiolytic properties, gepirone has been found to improve symptoms of sexual dysfunction in men and women, similarly to the marketed 5-HT1A receptor agonist flibanserin. The pro-sexual effects appear to be independent of its antidepressant and anxiolytic effects. Mechanism of action studies have demonstrated that gepirone possesses a much greater selectivity for 5-HT1A receptors over dopamine D2 receptors. Long-term studies have shown that gepirone has a differential action at presynaptic (agonist) and post-synaptic (partial agonist) 5-HT1A receptors. Treatment with gepirone ER desensitizes presynaptic 5-HT1A receptors, which decreases serotonin autoregulatory inhibition and enhances activation of postsynaptic 5-HT1A receptors. As a partial agonist gepirone ER acts as an agonist when endogenous serotonin is not present and as an antagonist when endogenous serotonin is present. Overall, gepirone ER increases serotonin production when insufficient amounts are present, and decreases serotonin production when excess amounts are present. Gepirone has been tested in Phase II clinical trial as antidepressant medication for pharmacotherapy for cocaine dependent subjects.

CAPTODIAME, also known as captodiamine, is a diphenylmethane derivative. It is a 5-HT2c receptor antagonist and agonist at sigma-1 and D3 dopamine receptors. It is an antihistamine which is used as a sedative and anxiolytic. CAPTODIAME is probably useful in preventing benzodiazepine withdrawal syndrome.

Azacyclonol (aka gamma-pipradrol) is an ataractive agent; a compound which diminished hallucinations in psychotic individuals. It is sometimes referred to as a tranquilizer or antipsychotic, though it does not actually possess these properties. It was used in Europe during the 1950's for treatment of schizophrenia; likely to reduce the psychedelic effects of LSD and mescaline. However, it had mixed clinical effectiveness and did not gain widespread adoption and was eventually discontinued. Azacyclonol was sold under several trade names: Ataractan, Calmeran, Frenoton, Frenquel and Psychosan.

Zolazepam is used as an anaesthetic in veterinary medicine. Zolazepam is usually administered in combination with other drugs such as the NMDA antagonist tiletamine. This combination is indicated in cats for restraint or for anesthesia combined with muscle relaxation and in dogs for restraint and minor procedures of short duration requiring mild to moderate analgesia. Used alone, tiletamine does not provide adequate muscle relaxation for abdominal surgical procedures. When combined with zolazepam hydrochloride, good muscle relaxation is generally attained during the phase of deep surgical anesthesia.