Phenserine tartrate (phenserine), a phenylcarbamate analog of physostigmine, is a long-acting and centrally active inhibitor of acetylcholinesterase (AChE). In addition to being a potent inhibitor of AChE, it has been demonstrated that phenserine inhibits the formation of beta-APP, the source of neurotoxic beta-amyloid peptide which is a major component of the extraneuronal plaques that pathologically characterize Alzheimer’s disease (AD). Phenserine was developed as a potential therapy for AD by Axonyx, under license from the National Institutes of Health/National Institute on Aging. In March 2005, Axonyx suspended patient recruitment for the ongoing Phase III trials of phenserine, after the drug failed to meet the primary endpoints of the first of these trials.

WAY-181187 is a high affinity and selective 5-HT6 agonist. It displays 60-fold selectivity over other 5-HT and monoamine receptors. WAY-181187 stimulates cAMP, ERK1/2 and Fyn kinase signaling pathway through serotonin receptor activation. WAY-181187 produced both antidepressant-like and anxiolytic-like effects in the animal model. It had been in phase I clinical trial for the treatment of anxiety disorders but this research has been discontinued.

L-822179 is a triazolophthalazine that selectively attenuates the effects of GABA at GABA(A) receptors containing an alpha5 subunit. It is an orally active, functionally selective compound, which enhances cognition in animals without anxiogenic or convulsant effects. The dose-limiting adverse event of L-822179 is dizziness and/or light-headedness. L-822179 does not improve cognitive performance in the elderly; indeed the dose of 4 mg actually significantly impairs performance. In this regard, it could therefore be considered that this study is a failed trial in so far as the positive control, lorazepam, does not show the anticipated effect.

RS-127445 is a selective; high affinity; orally bioavailable serotonin 5-HT2B receptor antagonist. RS-127445 was found to have a nanomolar affinity for the 5-HT2B receptor (pKi = 9.5 /-0.1) and 1,000 fold selectivity for this receptor as compared to numerous other receptors and ion channel binding sites. RS-127445 potently antagonized 5-HT-evoked formation of inositol phosphates (pK(B) = 9.5 /-0.1) and 5-HT-evoked increases in intracellular calcium (pIC50 = 10.4 /-0.1). RS-127445 also blocked 5-HT-evoked contraction of rat isolated stomach fundus (pA2 = 9.5 /-1.1) and ( /-)alpha-methyl-5-HT-mediated relaxation of the rat jugular vein (pA2 = 9.9 /-0.3). RS-127445 (MT-500) was being developed for the prophylactic treatment of migraine. POZEN acquired MT-500 from Roche in November 1999 and assumed full responsibility for its development for migraine prophylaxis.

LY-288513 is a selective CCK2 receptor antagonist (IC50 values are 16 and > 30,000 nM for CCK2 and CCK1 respectively). LY-288513 displays anxiolytic and antipsychotic properties in vivo.

Pircotoxinin is a component of pircotoxin, a poisonous compound from Anamirta cocculus. It exerts its action by blockade of anion channels, such as GABA-A or GlyR.

SB-271046 is one of the first selective 5-HT6 receptor antagonists to be discovered. SB-271046 is a potent, selective and orally active 5-HT6 receptor antagonist with a pKi value of 8.9. This compound provides a useful tool for further elucidating the physiological function of 5-HT6 receptors in vivo. SB-271046 was found to increase levels of the excitatory amino acid neurotransmitters glutamate and aspartate, as well as dopamine and noradrenaline in the frontal cortex and hippocampus of rats, and 5-HT6 antagonists have been shown to produce nootropic effects in a variety of animal studies. Suggested applications of SB-271046 included treatment of schizophrenia and other psychiatric disorders. A phase I clinical development of SB-271046 by GlaxoSmithKline (GSK) was discontinued due to a poor BBB permeability.

DOXYLAMINE CHLOROTHEOPHYLLINATE is a combination of two drugs doxylamine and 8-chlorotheophylline. Doxylamine is a first-generation antihistamine, that have short-term sedative effect. 8-Chlorotheophylline, a chlorinated derivative of theophylline, was added in order to counteract drowsiness. Doxylamine Chlorotheophyllinate can be used to treat motion sickness and nausea.

Umbelliferone is a natural product of the coumarin family which can be found in many different plant species. It absorbs ultraviolet light strongly at several wavelengths and is used in sunscreens. It has also been reported to have antioxidant, anti-inflammatory, and anti-nocioceptive properties.

Quercitrin is known as a bio flavonoid antioxidant and was investigated extensively in its antioxidant potential in streptrozotocin (STZ)-induced diabetic rats. Quercitrin is also a constituent of the dye quercitron. Quercitrin can be found in Tartary buckwheat and in oaks species such as white oak or European red oak. Quercitrin has potential anti-inflammation effect that is used to treat heart and vascular conditions. Quercitrin offers protection against brain injury in mice by inhibiting oxidative stress and inflammation. Quercitrin also prevented CCl4 induced cerebral function disorders associated with its ability to inhibit the activities of monoamine oxidase (MAO), acetylcholine esterase (AChE) and the N-methyl-d-aspartate receptor 2B subunit (NR2B). Quercitrin suppressed the release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Quercitrin may be a potential candidate to be developed as a neuroprotective agent. Quercitrin has been used previously as an antibacterial agent and has been shown to inhibit the oxidation of low-density lipoproteins and prevent an allergic reaction. It was demonstrated that quercitrin exerts protective effects against H2O2-induced dysfunction in lung fibroblast cells. Quercitrin has antiproliferative and apoptotic effects on lung cancer cells by modulating the immune response. There were significant increases in caspase-3 activity, loss of MMP, and increases in the apoptotic cell population in response to quercitrin in DLD-1 colon cancer cells in a time- and dose-dependent manner. These results revealed that quercitrin has antiproliferative and apoptotic effects on colon cancer cells. Quercitrin activity supported with in vivo analyses could be a biomarker candicate for early colorectal carcinoma.