Perphenazine is a relatively high potency phenothiazine that blocks dopamine 2 receptors predominantly, but also may possess antagonist actions at histamine 1 and cholinergic M1 and alpha 1 adrenergic receptors in the vomiting center leading to reduced nausea and vomiting. The drug was approved by FDA for the treatment of schizophrenia and control of severe nausea and vomiting (either alone or in combination with amitriptyline hydrochloride). Perphenazine is extensively hepatic to metabolites via sulfoxidation, hydroxylation, dealkylation, and glucuronidation; primarily metabolized by CYP2D6 to N-dealkylated perphenazine, perphenazine sulfoxide, and 7-hydroxyperphenazine (active metabolite with 70% of the activity of perphenazine) and excreted in the urine and feces.

Hydroxyzine, a piperazine antihistamine structurally related to buclizine, cyclizine, and meclizine, is used to treat histamine-mediated pruritus or pruritus due to allergy, nausea and vomiting, and, in combination with an opiate agonist, anxiolytic pain. Hydroxyzine is also used as a perioperative sedative and anxiolytic and to manage acute alcohol withdrawal. Hydroxyzine competes with histamine for binding at H1-receptor sites on the effector cell surface, resulting in suppression of histaminic edema, flare, and pruritus. The sedative properties of hydroxyzine occur at the subcortical level of the CNS. Secondary to its central anticholinergic actions, hydroxyzine may be effective as an antiemetic. It is used for symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested.

Meprobamate is a carbamate derivative used as an anxiolytic drug. Meprobamate enhances GABA-A currents, and at higher concentration, exhibits a separate channel-blocking effect that limits the magnitude of GABA(A) receptor potentiation. It is also a potent adenosine reuptake inhibitor (AdoRI), which is most likely responsible for its lesser degree of sedation compared to barbiturates. Meprobamate was withdrawn from European and Canadian markets due to its potential to cause physical and psychological dependence.

Pentobarbital belongs to the class of a short-acting barbiturate is used as sedatives, hypnotics, for the short-term treatment of insomnia, since they appear to lose their effectiveness for sleep induction and sleep maintenance after 2 weeks; preanesthetics and anticonvulsant, in anesthetic doses, in the emergency control of certain acute convulsive episodes, e.g., those associated with status epilepticus, cholera, eclampsia, meningitis, tetanus, and toxic reactions to strychnine or local anesthetics. Pentobarbital binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission.

Phenobarbital is a barbiturate derivative used to treat insomnia and anxiety, seizures, hyperbilirubinemia in neonates and cholestasis. Phenobarbital promotes binding to inhibitory gamma-aminobutyric acid subtype receptors, and modulates chloride currents through receptor channels.

A sulfide ion is composed of a lone sulfur atom. Its charge is negative two, giving sulfides this formula: S^2-. Sulfide is a strong base, so solutions of sulfide in water are basic, due to hydrolysis. One well-known ionic compound with a sulfide ion is H_2S. The infamous rotten-egg smell often associated with sulfur originates from this compound. Sodium sulfide nonahydrate is used in the formation of surface functionalized cadmium sulfide quantum dots.

Coluracetam (code name BCI-540; formerly MKC-231) is a nootropic agent of the racetam family. It was initially developed and tested by the Mitsubishi Tanabe Pharma Corporation for Alzheimer's disease. After the drug failed to reach endpoints in its clinical trials it was in-licensed by BrainCells Inc for investigations into major depressive disorder (MDD). Like most racetam compounds, Coluracetam increases choline uptake, but it also increases uptake in damaged neurons. Specifically, Coluracetam interacts with the HACU process, which is responsible for absorbing choline into the neurons. This increased uptake occurs during the Acetylcholine synthesis process. Since Coluracetam improves choline preservation during this process, a larger amount is converted into Acetylcholine. This results in increased memory, attention and alertness. It is important to note here, that these benefits were only seen in subjects with previously impaired neurons, not in subjects with normally functioning neurons. Coluracetam is also shown to improve AMPA potentiation, which is a process that triggers cognitive function and alertness. Although Coluracetam interacts with choline transporters as well, there isn’t enough evidence to explain why or how this interaction occurs, or what occurs after the interaction. Coluracetam has been in phase II clinical trials for the treatment of major depression and anxiety. However, this research has been discontinued.

AstraZeneca (formerly Astra) is developing robalzotan (NAD-299, AZD-7371), a 5-HT1A antagonist, for the potential treatment of depression and anxiety. The compound has entered phase II trials but was discontinued. Then it investigated for the treatment of irritable bowel syndrome, but the study was prematurely terminated. The same final has expected the development of robalzotan in phase II to treat overactive bladder, this investigation was terminated in July 2005.

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.

Sunepitron (CP-93,393) is an anxiolytic drug with highly selective serotonin 5-hydroxytryptamine 1A autoreceptor agonist, alpha2-adrenergic antagonist, and dopamine D2 agonist properties. Sunepitron hydrochloride had been in Phase III clinical trials by Pfizer for the treatment of anxiety disorder and depression. However, this research has been discontinued.