Allopregnan-3α-ol-20-one acetate (5α-Pregnan-3β-ol-20-one 3β-acetate) is a derivative of neurosteroid Allopregnanolone. Allopregnan-3α-ol-20-one acetate is an allosteric modulator of inhibitory γ-aminobutyric acid (GABA-A) receptors on neural stem cells and other cell types in the brain. Allopregnanolone acetate exerted moderate antidystonic effects and provoked a moderately reduced locomotor activity in animal models. Metabolic transformation of Allopregnan-3α-ol-20-one acetate leads Allopregnanolone. Allopregnanolone is in phase III trials for the treatment of super-refractory status epilepticus (SRSE) and postpartum depression, but Allopregnan-3α-ol-20-one acetate was never tested in clinical trials.

1-Hydroxymidazolam (Alpha-hydroxy-midazolam) is pharmacologically active midazolam metabolite, which is, like the parent drug midazolam a neuronal depressant drug. There are numerous studies in which the statements concerning the contribution of 1-Hydroxymidazolam to the clinical actions of midazolam range from “almost equipotent” to “no major contributing factor”. In humans, Hydroxymidazolam is subject to further glucuronidation, followed by renal excretion. In humans, urinary recovery of 1-Hydroxymidazolam glucuronide accounted for 60 to 70% of an administered dose of [14C]midazolam. 1-Hydroxymidazolam and it’s glucuronide were found in patients with renal failure after administration of midazolam and may account for the prolonged sedation observed in those patients.

ADX-47273 is a research pharmaceutical developed by Addex Therapeutics. It is a novel positive allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5). ADX-47273 displays antipsychotic, neuromodulatory, and cognition enhancing activities. In vivo, ADX 47273 increases waking and decreases deep sleep behaviors; it also increases late phase long-term potentiation (LTP) and enhances adaptive learning. In other animal models, ADX-47273 decreases amphetamine- and phencyclidine-induced hyperlocomotion and accumbal dopamine levels.

LY2033298 is a selective allosteric modulator for muscarinic acetylcholine M4 receptor. It exerts antipsychotic action in animal models. The compound is able to modulate circadian activity rhythms and morphine-induced conditioned place preference in rats.

α-Hexachlorcyclohexane a byproduct of a production of insecticide lindane (γ-hexachlorocyclohexane). α-Hexachlorcyclohexane is a major (60-70%) component of technical grade hexachlorocyclohexane. It is a widespread environment pollutant and cause liver tumors in rats and mice.

Imidazenil is an imidazo-benzodiazepine derivative with high intrinsic efficacy and selectivity for α2-, α3-, and α5- but low intrinsic efficacy for α1-containing GABA(A) receptors. It has an unusual profile of effects, producing some of the effects associated with normal benzodiazepines such as anticonvulsant and anxiolytic effects, yet without any notable sedative or amnestic effects. It has been suggested as a safe and effective treatment for anxiety, a potent yet non-sedating anticonvulsant and as a novel treatment for schizophrenia.

24S-hydroxycholesterol (24(S)-HC), the major cholesterol metabolite in the brain, is critical to brain cholesterol metabolism and turnover. This metabolite is a very potent, direct, and selective positive allosteric modulator of N-methyl-D-aspartate receptors (NMDARs) with a mechanism that does not overlap that of other allosteric modulators. NMDARs are glutamate-gated ion channels that are critical to the regulation of excitatory synaptic function in the CNS. It is known, that concentrations of 24(S)-HC in plasma and cerebrospinal fluid (CSF) are significantly higher in Alzheimer's disease and in mild cognitive impairment patients at early stages of the diseases compared to healthy subjects. It was suggested, that 24-hydroxycholesterol, could be a sensitive biomarker for the evaluation of these two diseases.

6-Hydroxyflavone is a naturally occurring flavone found in the leaves of Barleria prionitis, a plant species in the Acanthaceae family native to India that is widely used against neurological disorders such as paraplegia, sciatica, etc. 6-Hydroxyflavone partially potentiated GABA-induced currents in native GABAA receptors expressed in cortical neurons via BZ site, as the enhancement was blocked by the antagonist flumazenil. Furthermore, in patch clamp studies, 6-Hydroxyflavone displayed the significant preference for a2- and a3- containing subtypes, which were thought to mediate anxiolytic effect, compared to a1- and a5- containing subtypes expressed in HEK 293T cells. In mice, 6-Hydroxyflavone exhibited the anxiolytic-like effect in the elevated plus-maze test, unaccompanied at anxiolytic doses by the sedative, cognitive impairing, myorelaxant, motor incoordination and anticonvulsant effects commonly associated with classical BZs when tested in the hole-board, step-through passive avoidance, horizontal wire, rotarod, and pentylenetetrazol (PTZ)-induced seizure tests, respectively. The findings, therefore, identified 6-Hydroxyflavone as a promising drug candidate for the treatment of anxiety-like disorders.