PK-11195 is a selective antagonist of the Translocator Protein (TSPO). The C11 radiolabeled isotope of PK-11195 ([11C]-(R)-PK-11195) has been used effectively for diagnostic PET imaging in a number of CNS conditions where imaging of TSPO is informative (the S- enantiomer is not used). Applicable conditions including Schizophrenia, Multiple Sclerosis, and Traumatic Brain Injuries where it has been particularly useful for detection of increased microglial activation. It has also been investigated as means to monitor the role of Toll-Like Receptor-4 (TLR-4) after cerebral ischemia in mice. It should be noted that the unlabeled PK-11195 had been investigated for a number of potential therapeutic uses but did not progress beyond animal and cell models.

Y-33075 is potent and selective ROCK (Rho-associated coiled-coil-forming protein kinase) inhibitor, developed by Yoshitomi Pharmaceutical Industries for encephalomyelitis treatment. In rabbits and in monkeys, Y-33075 lowers IOP in a dose-dependent fashion. An increase in regenerating axons of RGCs in 100 mM Y-33075-treated eyes is observed compared with saline-treated eyes. Y-33075 dose-dependently increases the number of RGCs with regenerating axons. Both Y-33075 induces a concentration-dependent relaxation in rabbit ciliary arteries precontracted with a high-potassium (high-K) solution. The amplitude of relaxation induced by Y-33075 is not affected by either 100 μM N (G)-nitro-L: -arginine methyl ester (L: -NAME) or 10 μM indomethacin. In Ca2 -free solution, Y-27632 and Y-39983 significantly inhibit the transient contraction of ciliary arteries induced by 10 μM histamine. However, neither Y-27632 nor Y-39983 affects the elevation of [Ca2 ](i) induced by high-K solution and histamine.

PNU-109291 is a potent and selective 5HT1D receptor agonist. PNU-109291 was able to block neurogenic inflammation in the guinea pig model of migraine.

4,4'-Thiodianiline is a chemical intermediate that was used in a production of mordant yellow and other dyes. 4,4'-Thiodianiline is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. 4,4'-Thiodianiline has demonstrated anticonvulsant activity in vivo.

MRK-409 (MK-0343) is a subtype-selective GABA(A) partial agonist that occupies the benzodiazepine site of GABA(A) receptors. MK-0343 was designed to be a less sedating anxiolytic, based on reduced efficacy at the alpha-1 subtype and significant efficacy at alpha -2 and alpha-3 subtypes of the GABA(A) receptor. MRK-409 binds to alpha-1, 2, 3 and 5-containing human recombinant GABA(A) receptors with comparable high affinity (0.21-0.40 nM). However, MRK-409 has greater agonist efficacy at the alpha-3 compared with alpha-1 subtypes. MRK-409 exhibited anxiolytic and non-sedating properties in different rodent and primate models of unconditioned and conditioned models of anxiety but produced sedation in man at relatively low levels of GABA(A) receptor occupancy (∼10%). It was suggested that the sedation with MRK-409 was due to the partial agonist efficacy of that compound at the alpha-1 subtype. Although MRK-409 (MK-0343) reached clinical studies its development had to be stopped due to sedative effects in humans demonstrated that more preclinical efforts are needed to identify compounds with improved selectivity.

Picrotin is a component of picrotoxin, an equimolar mixture of picrotoxinin and picrotin, which was isolated from the fruit of Anamirta cocculus. Picrotin is inactive in inhibiting the GABA-A and GABA-C receptors, but the compound is able to block homomeric alpha1 and alpha1 beta glycine receptors. Picrotoxin is used as an antidote to severe barbiturate poisoning, however picrotin does not participate in the activity. Picrotin is not toxic.

CI-966 is a GABA reuptake inhibitor, acting as an indirect and nonselective GABA agonist by blocking GABA transporter protein GAT-1. CI-966 was investigated in phase I clinical study for treatment of epilepsy, but its development was discontinued due to physical and mental disturbances at high doses.

LY-334370 is a selective agonist at the serotonin 1F receptor. Lilly had been conducting phase II clinical testing of this compound in Europe as a potential therapy for migraine headaches. Lilly has now announced that it has discontinued commercial development of LY 334370 as a result of a review of data from an ongoing animal toxicology study. It was reported that the compound causes G-protein activation that is mediated by 5-HT1A receptors.

L-760735 is a non-peptide substance P receptor (Neurokinin 1 (NK1) receptor) antagonist. It exerts anxiolytic, antidepressant and antinociceptive actions in animals. Merck was developing an L- 760735 as a potential antidepressant.

CGS-20625 is a potent and selective ligand for the central benzodiazepine receptor. It acts as a partial agonist of GABAA channel in vitro and produces anxiolytic and anticonvulsant effects in vivo. The drug has low bioavailability so its clinical applications are limited, and it is mainly used as a tool compound.