GRN-529 is a negative allosteric modulator of mGluR5. In a mouse model of autism, GRN-529 (named as PF-05212391 by Pfizer) decreased self-grooming and stereotyped jumping and increased social functioning compared with no treatment. In a mouse model of depression, GRN-529 had dose-dependent efficacy across a therapeutically relevant battery of animal models, comprising depression and 2 of the co-morbid symptoms overrepresented in treatment resistant depression, namely anxiety and pain

Smoothened agonist (SAG), a chlorobenzothiophene-containing Hh pathway agonist, was shown to be able to bind directly to Smo and activate Shh-dependent pathway. SAG and similar compounds represent attractive molecules to be developed for treatment of disorders where stimulation of the generation and survival of new neural cells would be beneficial. Thus, it was demonstrated that small-molecule agonist of Smo has potential as a neuroprotective agent in neonates at risk for glucocorticoid-induced neonatal cerebellar injury. Moreover, hedgehog agonist therapy corrects structural and cognitive deficits in a Down syndrome mouse model.

PD 144418 oxalate is a remarkably potent and selective sigma1 receptor ligand having potential antipsychotic properties. PD 144418 oxalate displayed an apparent affinity (Ki) of 0.08 nM for sigma1 sites in guinea pig brain membranes and a Ki of 1377 nM for sigma2 sites in rodent neuronal NG108-15 cell membranes. PD 144418 oxalate was classified as sigma1 receptor antagonist based upon several assays, including the ability to attenuate mescaline-induced scratching in mice. PD 144418 oxalate attenuates cocaine-induced hyperactivity in mice. It showed potential antipsychotic activity, but no antidepressant or anxiolytic actions.

PEAQX (NVP-AAM 077) is a potent and orally active NMDA antagonist with a 15-fold preference for human NMDA receptors with the 1A/2A(IC50=270 nM), rather than 1A/2B (29,600 nM). Animals treated with PCP or PEAQX on PN7, PN9, and PN11 showed a sensitized locomotor response to PCP challenge on PN28-PN35. PEAQX induced social suppression in rats.

3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA), a drug used for the treatment of Parkinson's disease patients. 3-OMD is formed by catechol-O-methyltransferase. 3-OMD may be responsible for the side effects of L-DOPA.

SB-699551 is the first selective serotonin 5A receptor antagonist. SB-699551 showed an anxiolytic-like property in animal model. It demostrated efficacy against schizophrenia-like cognitive deficits and negative symptoms in rats. Blockade of 5-HT5A receptor with SB-699551 appear to be able to impair the consolidation of memory in rodents. In addition, 5-HT-induced spinal antinociception in the capsaicin and acetic acid tests was blocked by SB-699551.

BMS-299897 is an orally bioavailable, sulfonamide γ-secretase inhibitor with an IC50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP). BMS-299897 has the potential for treatment of Alzheimer's disease.

MCOPPB trihydrochloride (MCOPPB) is a nonpeptide agonist of the NOP receptor, an anxiolytic agent. MCOPPB has a high affinity for the human NOP receptor (pKi = 10.07 +/- 0.01) and selectivity for the NOP receptor over other members of the opioid receptor family: 12-, 270- and >1000-fold more selective for the NOP receptor than for the micro-, kappa-, and delta-receptor, respectively. In an ex vivo binding study, MCOPPB (10 mg/kg, p.o.) inhibited signaling through the NOP receptor in the mouse brain, suggesting that it penetrated into the brain after it was orally administered. MCOPPB - a compound with few adverse effects on the central nervous system - is a potential therapeutic agent for the treatment of anxiety.

CDPPB is a drug used in scientific research which acts as a positive allosteric modulator (PAM) selective for the metabotropic glutamate receptor subtype mGluR5 CDPPB was shown to be the first systemically available mGlu5 PAM, thus allowing for behavioral assessment in antipsychotic models, including reversal of amphetamine-induced hyperlocomotion and reversal of deficits in prepulse inhibition, both of which have translational validity in patients with schizophrenia eliciting positive symptoms and cognitive deficits in sensorimotor gating, respectively. CDPPB was shown to be efficacious in both of these models at moderate subcutaneous (s.c.) doses between 10 and 30 mg/kg. Numerous in vivo studies using CDPPB have recently surfaced which continue to add evidence and support for the potential to treat CNS disorders associated with aberrant NMDA receptor function, including the cognitive impairments and negative symptoms of schizophrenia.

SR-57227A is a potent and selective agonist at the 5HT3 receptor, with high selectivity over other serotonin receptor subtypes and good blood-brain barrier penetration. SR-57227A had affinities (IC50) varying between 2.8 and 250 nM for 5-HT3 receptor binding sites in rat cortical membranes and on whole NG 108-15 cells or their membranes in vitro. SR 57227A stimulated the uptake of [14C]guanidinium into NG 108-15 cells in the presence of substance P and contracted the isolated guinea-pig ileum, effects that were antagonized by the 5-H 3 receptor antagonist tropisetron. The agonist effect of SR 57227A was also observed in vivo, as the compound elicited the Bezold-Jarisch reflex in anesthetized rats, an effect that was blocked by tropisetron.