cognitive dysfunction

Parecoxib (SC 69124) is an effective and selective COX-2 inhibitor.

Cefazolin sodium (cephazolin sodium) salt binds to and inactivates penicillin-binding proteins (PBP) located on the inner membrane of the bacterial cell wall. Cefazolin sodium salt is the sodium salt of cefazolin, a beta-lactam antibiotic and first-generation cephalosporin with bactericidal activity. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity, which results in the weakening of the bacterial cell wall and cell lysis.

Amantadine hydrochloride (CI-719) is an antiviral that is used in the prophylactic or symptomatic treatment of influenza A and Parkinson disease.

Amantadine (1-Aminoadamantane) is an antiviral, is a weak antagonist of the NMDA-type glutamate receptor, increases dopamine release, and blocks dopamine reuptake.

Cefazolin is a semi-synthetic cephalosporin that has a broad spectrum of antibacterial activity and inhibits the synthesis of bacterial cell walls.

10β,17β-dihydroxyestra-1,4-dien-3-one (DHED) is a brain-selective prodrug of 17β-estradiol, which has neuroprotective effects, improves cognitive dysfunction, and can be used to study brain damage.

GSK-239512 is an antagonist of H3 receptor and can be used in studies about the treatment of cognitive dysfunction in neurodegenerative disorders.

SKF83959, a benzazepine analog, is a selective and potent partial agonist of the dopamine D1 receptor with Ki values of 1.18, 7.56, 920, and 399 nM for rat D1, D5, D2, and D3 receptors, respectively.SKF83959 is a potent variant modulator of the sigma (σ)-1 receptor, which ameliorates cognitive dysfunction for the study depression and Alzheimer's disease.

Dalzanemdor (SAGE-718) is a selective, orally active NMDA receptor (N-methyl-D-aspartate receptor) modulator. By modulating NMDA receptor function, Dalzanemdor enhances glutamatergic neurotransmission, thereby improving neural network activity. Dalzanemdor is being investigated for use in the treatment of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease.

Sarcosine (Methylglycine) is a competitive inhibitor of the type I glycine transporter (GlyT1) and an N-methyl-D-aspartate receptor (NMDAR) co-agonist.

Mirisetron (WAY-100579, SEC-579) is an indole-based 5-HT3 receptor antagonist exhibiting cognitive-enhancing effects. It counteracts learning deficits associated with central cholinergic neuronal dysfunction and may be employed in studying neurological disorders such as Alzheimer's disease.

Paxilline is an indole alkaloid mycotoxin from *Penicillium paxilli*, acting as a potent BK channel inhibitor via an almost exclusively closed-channel block mechanism. Paxilline possesses significant anticonvulsant activity.

Lecozotan (SRA-333) is a potent and selective 5-HT antagonist developed for Alzheimer's disease treatment. This compound significantly increases the release of glutamate and acetylcholine in the hippocampus and dentate gyrus areas upon potassium ion stimulation, exhibiting cognitive enhancement properties. Long-term use of Lecozotan does not lead to tolerance or dysfunction of the 5-HT(1A) receptor, demonstrating its stable pharmacological properties. Additionally, acute administration can improve learning and memory abilities in rats without affecting their anxiety levels or behavior depression.

CUR-IPA is a cholinesterase inhibitor with IC50 values of 5.99 μM for eAChE (electric eel), 59.30 μM for hAChE (human), and 60.66 μM for hBChE (human). It has free radical scavenging and antioxidant activity and is useful for researching cognitive dysfunction.

Z-4105 (formula l) is a nootropic compound. It reverses the amnesia effects induced by electroconvulsive shock (ECS) and methylazoxymethanol acetate (MAM), thereby improving learning and memory functions. The compound enhances the activity of the brain's cholinergic system without affecting other neurotransmitter systems. Additionally, Z-4105 significantly alleviates neuropathic pain caused by chronic constriction injury (CCl) in rat sciatic nerve and spinal nerve ligament models. It is utilized in research on neuropathic pain and cognitive dysfunction.

T 588 is an orally active neuroprotective agent that enhances acetylcholine release in the frontal cortex and hippocampus, thereby improving cognitive dysfunction. It safeguards cerebellar granule cells from glutamate-induced neurotoxicity and is applicable in neurological research, including studies on Alzheimer's disease.

PZ-1657 (Compound 57) is an orally active inverse agonist of the 5-HT7 receptor (5-HT7 receptor), with high selectivity, ability to penetrate the blood-brain barrier, and metabolic stability, demonstrating a Ki value of 5 nM. It effectively inhibits Gs pathway-mediated basal cyclic adenosine monophosphate (cAMP) production, with an EC50 value of 2.93 nM. Additionally, PZ-1657 inhibits CYP3A4P450 (IC50 = 12.2 μM) and affects the hERG channel. This compound also reduces MMP-9 activity mediated by the 5-HT7 receptor and reverses cognitive dysfunction induced by Phencyclidine. PZ-1657 exhibits antidepressant properties.

BChE-IN-46 is a selective BChE inhibitor with the ability to penetrate the blood-brain barrier [eqBChE IC50 = 7.44 × 10^-5 μM, SI > 270,000, hBChE IC50 = 1.48 × 10^-3 μM]. It also exhibits COX-2 inhibitory activity (IC50 = 0.11 μM). BChE-IN-46 may offer neuroprotective effects, enhance acetylcholine levels, and improve cognitive dysfunction, anxiety, as well as learning and memory deficits. It is a potential candidate for the development of anti-Alzheimer's disease drugs.

CI-1002 is a novel anticholinesterase and muscarinic antagonist that can be used to treat cognitive dysfunction in AD with fewer peripheral side effects.

OAB-14 is a Bexarotene derivative that improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice. OAB-14 effectively ameliorates the dysfunction of the endosomal-autophagic-lysosomal(EAL) pathway in APP/PS1 transgenic mice [1] [2].

Selective sigma (σ) receptor ligand. Displays high affinity for σ1; also binds at σ2 sites (Ki = 1.5 nM and 50.8 nM respectively). Selective over a range of receptor types including dopaminergic and muscarinic receptors, DAT and SERT. Prezzavento et al (2007) Novel sigma receptor ligands: synthesis and biological profile. J.Med.Chem. 50 951 PMID:17328523 |Prezzavento et al (2008) A new sigma ligand, (±)-PPCC, antagonizes kappa opioid receptor-mediated antinociceptive effect. Life Sci. 82 549 PMID:18261749 |Antonini et al (2009) Anti-amnesic properties of (±)-PPCC, a novel sigma receptor ligand, on cognitive dysfunction induced by selective cholinergic lesion in rats. J.Neurochem. 109 744 PMID:19245662

MY33-3 is a powerful and specific inhibitor of receptor protein tyrosine phosphatase (RPTP)β/ζ, demonstrating an IC50 value of approximately 0.1 μM. Moreover, MY33-3 exhibits inhibitory activity against PTP-1B with an IC50 value of about 0.7 μM. Additionally, MY33-3 has been shown to effectively decrease ethanol consumption and alleviate neuroinflammation and cognitive dysfunction induced by Sevoflurane.

MY33-3 hydrochloride is a potent and selective inhibitor of the protein tyrosine phosphatase RPTPβ/ζ (IC50~0.1 μM) and PTP-1B (IC50~0.7 μM). It also reduces ethanol consumption and alleviates Sevoflurane-induced neuroinflammation and cognitive dysfunction.

Usmarapride is a potent and selective 5‑HT₄ receptor partial agonist (EC₅₀ = 27.5 nM) with oral bioavailability and blood–brain barrier penetrability, suitable for research on cognitive dysfunction associated with Alzheimer’s disease.