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S 18986 is a selective, orally active, brain-penetrant positive allosteric modulator of AMPA-type receptors that enhances cognition in rodents by inducing the release of noradrenaline and acetylcholine in the rat hippocampus, subsequently improving object-recognition memory.

THPP-1 is a potent and orally bioavailable inhibitor of PDE10A(Ki of 1 nM and 1.3 nM for human and rat PDE10A, respectively).

VU6024578 (BI02982816) is an orally bioavailable and selective positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR1. It demonstrates activation with EC50 values of 54 nM for human mGluR1 and 46 nM for rat mGluR1. VU6024578 shows antipsychotic activity in rat models of amphetamine-induced hyperactivity and MK-801-induced novel object recognition (NOR). Additionally, it possesses blood-brain barrier permeability.

DNS-8254 is a potent and selective Phosphodiesterase 2 (PDE2) inhibitor for the treatment of Memory Disorders (hPDE2a IC50 = 8 nM, Rat Cl-int = 25.6 uL/min/mg). DNS-8254 demonstrated significant memory enhancing effects in a rat model of novel object reco

Donecopride is a partial agonist of the serotonin (5-HT) receptor subtype 5-HT4E(Ki= 8.5 nM) and an inhibitor of acetylcholinesterase (AChE; IC50= 16 nM).1It is selective for AChE over butyrylcholinesterase (BChE; IC50= 3,530 nM) but does bind to 5-HT2Band sigma-2 (σ2) receptors (Ki= 1.6 nM for both) in a panel of 42 neurotransmitter receptors and transporters. Donecopride induces release of soluble amyloid precursor protein-α (sAPP-α) in COS-7 cells transiently expressing 5-HT4with an EC50value of 11.3 nM. Oral administration of donecopride (1 mg/kg) reduces brain soluble and insoluble amyloid-β (1-42) levels and increases the time spent exploring the novel object in the novel object recognition (NOR) test in the 5XFAD transgenic mouse model of Alzheimer's disease. Donecopride (3 mg/kg, p.o.) prevents a reduction in spontaneous alternation behavior induced by intracerebroventricular administration of soluble Aβ42 (sAβ42) in the Y-maze in mice.2 1.Lecoutey, C., Hedou, D., Freret, T., et al.Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatmentProc. Natl. Acad. Sci. USA111(36)E3825-E3830(2014) 2.Rochais, C., Lecoutey, C., Hamidouche, K., et al.Donecopride, a Swiss army knife with potential against Alzheimer's diseaseBr. J. Pharmacol.177(9)1988-2005(2020)

UoS 12258 is a selective and efficient AMPA receptor positive allosteric modulator, reversing acute and subacute drug-induced deficits in rat novel object recognition, used to study cognitive disorders.

Amyloid-β (25-35) (Aβ (25-35)) is an 11-residue fragment of the Aβ protein that retains the physical and biological characteristics of the full length peptide. It forms fibrils that react to thioflavin T and Congo red and are organized in a cross-β arrangement of β-strands similar to Aβ (1-40) and Aβ (1-42) fibrils. Aggregated Aβ (25-35) decreases the viability of rat adrenal PC12 cells. It also decreases the viability of primary rat cortical neurons at concentrations ranging from 1 nM to 30 μM. In vivo, intracerebral injection of Aβ (25-35) (20 nmol) in rats induces lesions of neuronal and tissue loss. Aggregated Aβ (25-35) administered intracerebroventricularly to rats induces learning and memory impairments in the Y-maze, novel object recognition, and contextual fear conditioning tests.

D159687 is a selective PDE4D inhibitor,had a procognitive profile as it improved memory in the novel object recognition test but had no antidepressant or anxiolytic benefit.

BAY-747 (BAY 1165747) is an orally administered, brain-penetrant compound that stimulates soluble guanylate cyclase (sGC). It effectively counteracts memory impairments induced by L-NAME, improves cognitive performance in rats during the object location task (OLT), reduces blood pressure in conscious normotensive and spontaneously hypertensive rats (SHR), and enhances skeletal muscle function in the mdx mTRG2 mouse model of Duchenne muscular dystrophy (DMD) [1] [2] [3].

PZ-1922 (Compound 16), able to cross the blood-brain barrier, is a dual antagonist for 5-HT6R and 5-HT3R with K i values of 17 nM and 0.45 nM, respectively. It also reversibly inhibits MAO-B with a pIC50 of 8.93. Moreover, PZ-1922 mitigates scopolamine (SCOP)-induced memory deficits in rats as observed in the novel object recognition (NOR) test and hinders Aβ-induced memory impairment in the T-maze test [1].

Dityrosine, an oxidation product of protein formed through the intermolecular cross-linking of tyrosyl radicals from the reactive oxygen species (ROS) and tyrosine interaction, is associated with decreased hippocampal expression of NMDA receptor subunits Nr1, Nr2a, and Nr2b when administered intragastrically at 320 µg kg per day, leading to memory impairments in mice as evidenced by their performance in a novel object recognition test. Additionally, it raises fasting blood glucose levels while reducing plasma insulin levels and the pancreatic expression of insulin synthesis-related genes Ins2, Pdx1, and MafA. Increased dityrosine levels have been positively linked to a range of diseases, including autism spectrum disorder, cataracts, Alzheimer's disease, Parkinson's disease, atherosclerosis, and cystic fibrosis.