GW-9508 is a small-molecule agonist of the fatty acid receptors GPR40 and GPR120. GW-9508 exerts wide-range activity in animal models: anti-depressant, anti-inflammatory, anti-diabetic and analgetic actions.

JNJ-31020028 was shown to have high affinity for both human and rodent Y2 receptors. The antagonistic property of JNJ-31020028 for the Y2 receptor was demonstrated via inhibition of PYY-stimulated calcium response in KAN-Ts cells expressing a chimeric G protein. After subcutaneous administration, the Y2 antagonist was found to penetrate into the brain and dose dependently occupy Y2 receptor binding sites, demonstrating that the compound engaged its target in the CNS. JNJ-31020028 (15 mg/kg, s.c.) did reverse the anxiogenic effects of withdrawal from a single bolus dose of alcohol on the elevated plus-maze, confirming the anxiolytic-like properties of Neuropeptide Y2 antagonism. JNJ-31020028 has antidepressant like effects in the olfactory bulbectomized model.

ATC-0065 is an oral antagonist of melanin concentrating hormone receptor 1. In preclinical testing ATC-0065 demonstrated anxiolytic and antidepressant activity.

Racemic phenibut (beta-phenyl-gamma-aminobutyric acid or 4-amino-3-phenylbutyric acid) is a neuropsychotropic drug that was discovered and introduced into clinical practice in Russia in the 1960s. In pharmacological tests of locomotor activity, antidepressant and pain effects, S-phenibut was inactive. In contrast, R-phenibut turned out to be two times more potent than racemic phenibut in most of the tests. Racemic phenibut and R-phenibut demonstrated an affinity for GABAB receptors, in contrast, S-phenibut was not able to bind receptors. Pharmacological activity of racemic phenibut relies on R-phenibut and this correlates to the binding affinity of enantiomers of phenibut to the GABAB receptor. Both S- and R-phenibut bind to the α2-δ subunit of voltage-dependent calcium channels and exert gabapentin-like anti-nociceptive effects. In addition S-isomer was found to be a substrate of gamma-aminobutyric acid aminotransferase, however, the R-isomer is a competitive inhibitor.

Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities.

8-Hyroxy-2-Dipropylaminotetralin Hydrobromide (8-OH-DPAT) is a chemical predominantly used in research settings. It is widely regarded as the first identified complete agonist of the 5-HT1a receptor, for which it has a Ki = 3.18 nM. 8-OH-DPAT also acts as an agonist of the 5-HT7 receptor, and as a substrate of the Sodium dependent serotonin transporter (SERT). Although it has never progressed to human clinical trials 8-OH-DPAT has been studied in animal models for a number of conditions both for its own potential and as a benchmark for other compounds.

Salidroside (Rhodioloside) is a glucoside which was isolated in 1926 from Salix triandra L. (Salicaceae). It is thought to be one of the compounds responsible for the antidepressant and anxiolytic actions of this plant, along with rosavin. Also was investigated that salidroside may be a promising candidate for the treatment of inflammatory liver injury and promotes skeletal regeneration in cell-autonomous and cell-non-autonomous ways and might be a potential therapy for accelerating fracture healing.

SCH-58261 is an antagonist of the Adenosine A2A receptor with a Kd of 2.3 nM. It was initially identified and developed by Schering-Plough as a potential treatment for neurological conditions such as Parkinson's Disease and Depression. However, the compound suffered from poor solubility and is not active when orally dosed. SCH-58261 became the scaffold for the development of Preladenant (SCH 412348), which did progress to Phase III clinical trials before being discontinued. There has also been an investigation of SCH-58261 as a treatment of hypotension in rat models.

LY404187 (or LY-404,187) is a selective, potent and centrally active positive allosteric modulator of AMPA receptors. LY404187 preferentially acts at recombinant human homomeric GluR2 and GluR4 versus GluR1 and GluR3 AMPA receptors. This drug, developed by Eli Lilly and Company, is a member of biarylpropylsulfonamides. LY404187 has been shown to enhance performance in animal models of cognitive function requiring different mnemonic processes and may be therapeutically beneficial for treating cognitive deficits in a variety of disorders, particularly those that are associated with reduced glutamatergic signaling such as schizophrenia. In addition, LY404187 has been demonstrated to be efficacious in animal models of behavioral despair that possess considerable predictive validity for antidepressant activity and Parkinson's disease.

S-14506 was originally identified and developed in France by Scientists at the Institut de Recherches Servier. S-14506 showed potent binding and antagonistic activity against the 5HT1-A receptor. It was found to work synergistically with D2 receptor antagonists and was therefore studied in animal models for depression, psychosis, and anxiety. A tritium labeled version was also studied as a potential 5HT1-A receptor PET imaging agent.