SB 202190 (FHPI) is a p38 MAPK inhibitor that inhibits p38α and p38β2 (IC50=50/100 nM) selectively and cell-permeably. SB 202190 has antitumor activity and also induces the differentiation of human embryonic stem cells into cardiomyocytes.

1. Orientin (Luteolin-8-glucoside) may be regarded as a candidate therapeutic agent for treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway. 2. Orientin protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. 3. Orientin has neuroprotection effect by the intracellular mediation of caspase activity; may alleviate cognitive deficits and oxidative stress in AD mice; can exert antidepressant-like effects on CUMS mice, specifically by improving central oxidative stress, neurotransmission, and neuroplasticity.

Y13g dihydrochloride is a potent inhibitor of interleukin 6 (IL-6) and acetylcholinesterase (AChE) (both targets of Alzheimer's disease (AD) progression are related). Y13g dihydrochloride reverses STZ-induced memory deficits and exhibits histopathology similar to normal animals.

Brexpiprazole HCl (OPC 34712 dihydrochloride) is a new antipsychotic drug.

Itasetron (U 98079A) is a 5-hydroxytryptamine 3-receptor antagonist used to prevent age-related memory deficits in rats.Itasetron's antiemetic activity in animal models of cancer chemotherapy and radiation therapy may be useful in the study of amnesia.

SAK3 is a novel modulator of nAChR activity that enhances T-type voltage-gated Ca2+ channel (T-VGCC) activity, and has potentiating effects on both Cav3.1 and Cav3.3 T-type Ca2+ channel currents.SAK3 is neuroprotective against scopolamine-induced cholinergic dysfunction in human neuroblastoma SH-SY5Y cells.SAK3 is used for the study of memory deficits and Alzheimer's disease. SAK3 can be used to study memory deficits and Alzheimer's disease.

MPT0G211 is a highly selective and orally active HDAC6 inhibitor (IC50=0.291 nM) that has neuroprotective effects and has shown anti-metastatic activity in human breast cancer cells. MPT0G211 has 1,000 times more affinity for HDAC6 than other HDAC subtypes. MPT0G211 can cross the blood-brain barrier and could be used to improve tau phosphorylation and cognitive deficits in Alzheimer's disease models.

PQCA is a muscarinic M1 receptor-positive allosteric regulator, which is highly selective and effective. PQCA exhibited EC50 values of 49 nM in rhesus monkey and 135 nM in human M1 receptors, but showed no activity against other muscarinic receptors. PQCA is a potential compound for reducing cognitive deficits associated with Alzheimer's disease.

PHA 543613 is a specific agonist of α7 nAChR (Ki = 8.8 nM) and can be used in studies about the cognitive deficits of Alzheimer's disease and schizophrenia.

GSK-872 (GSK2399872A) is an effective and specific RIP3 kinase inhibitor. It binds RIP3 kinase domain with high affinity (IC50: 1.8 nM) and inhibits kinase activity (IC50: 1.3 nM).

GPR139 agonist-2 (compound 20a), a potent GPR139 agonist with an EC50 of 24.7 nM, has demonstrated efficacy in rescuing social interaction deficits and alleviating cognitive deficits in murine schizophrenia models, indicating its potential in antischizophrenia drug research [1].

3'-sulfo Galactosylsphingosine is a form of sulfatide that is lacking the fatty acyl group. It decreases migration and adhesion of B35 neuroblastoma cells and increases cell rounding when used at a concentration of 20 μM. It also inhibits PKC and cytochrome c oxidase activity when used at concentrations of 150 and 50-100 μM, respectively. 3'-sulfo Galactosylsphingosine accumulates in patients with metachromatic leukodystrophy, a lysosomal storage disorder characterized by arylsulfatase A (ASA) deficiency leading to progressive demyelination and neuromotor deficits. In mice lacking ASA, levels of 3'-sulfo galactosylsphingosine increase after one month of age followed by demyelination and neuromotor deficits. 3'-sulfo Galactosylsphingosine has been used as a standard for the quantification of 3'-sulfo galactosylsphingosine by LC-MS.

Esculin sesquihydrate, a coumarin glucoside with fluorescent properties and a constituent of ash bark, improves cognitive deficits associated with experimental diabetic nephropathy (DN). It also offers anti-oxidative and anti-inflammatory benefits through the MAPK signaling pathway [1] [2].

Avermectin B1a aglycone is an aglycone form of the anthelmintic and insecticide avermectin B1a . It hyperpolarizes P. crassipes muscle fibers with a minimum active concentration (MAC) value of 0.1 μM. Avermectin B1a aglycone decreases survival of C. elegans (MAC = 0.1 μM). In vivo, avermectin B1a aglycone prevents seizures induced by pentylenetetrazole in mice (ED50 = 43.9 mg/kg) without inducing deficits in rotarod performance.

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].

(-)-GSK598809 hydrochloride is the isomer of GSK598809. GSK598809 is a selective antagonist of the dopamine D3 receptor (DRD3), which is a neural response that selectively enhances reward anticipation in drug and alcohol dependence during monetary policy and may repair reward deficits in substance dependence.

Glucocerebrosides are formed by the tethering of glucose to a ceramide by glucosylceramide synthase. They are present in neuronal and non-neuronal mammalian tissues and are found at low quantities in a large number of plant species. Glucocerebrosides are precursors in the synthesis of lactosylceramides and gangliosides. Increased levels of glucocerebrosides are associated with obesity-induced insulin resistance in mice and with neuronal deficits observed in neuronopathic Gaucher disease. This product is a mixture of glucocerebrosides, with variable ceramide chain lengths, isolated from a spleen of a human with Gaucher's disease.

nAChR agonist 1 (DUN71755) is a brain-permeable and orally efficacious positive allosteric α7 nicotinic acetylcholine receptor (α7 nAChR)modulator.

A-582941 dihydrochloride (A 582941) is a Selective agonist of α7 nAChR partial

Nrf2 Activator-8 (Compound 10e), with an EC50 of 37.9 nM, is a potent Nrf2 activator that demonstrates significant antioxidant and anti-inflammatory properties in BV-2 microglial cells. Furthermore, this compound notably ameliorates spatial memory deficits in a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation [1].

Unifiram is a nootropic agent.1It increases acetylcholine (ACh) release in the rat cerebral cortexin vivoand induces a long-lasting increase in the amplitude of field excitatory postsynaptic potentials (fEPSPs) in the rat hippocampal CA1 region (EC50= 27 nM). It does not bind to serotonin (5-HT), dopamine, muscarinic, nicotinic, adrenergic, glutamate, histamine, opioid, or GABA receptors at 1 μM. Unifiram (0.1 mg/kg) improves memory in non-memory-impaired rats in a social learning test.2It also prevents memory deficits induced by the anticholinergic agent scopolamine, nicotinic receptor antagonist mecamylamine, GABABreceptor agonist baclofen, or α2-adrenergic receptor agonist clonidine in the passive avoidance test in mice when administered at a dose of 0.01 mg/kg and prevents memory deficits induced by the AMPA/kainate glutamate receptor antagonist NBQX at 0.1 mg/kg.1 1.Romanelli, M.N., Galeotti, N., Ghelardini, C., et al.Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancersCNS Drug Rev.12(1)39-52(2006) 2.Ghelardini, C., Galeotti, N., Gualtieri, F., et al.The novel nootropic compound DM232 (unifiram) ameliorates memory impairment in mice and ratsDrug Develop. Res.56(1)23-32(2002)

Galactose prevents cognitive deficits in male Wistar rats.

PHA-543613 hydrochloride acts as a potent and selective agonist for the α7 subtype of neural nicotinic acetylcholine receptors, with a high level of brain penetration and good oral bioavailability. It is under development as a possible treatment for cognitive deficits in schizophrenia.

ASP-5854 is an adenosine A(2A) receptor antagonist with the potential to improve motor deficits in Parkinson's disease.

CM-414 is a dual inhibitor of HDACs and PDE5 for the Treatment of Alzheimer’s Disease (IC50 values of 60 nM, 310 nM, 490 nM, 322 nM, and 91 nM against PDE5, HDAC1, HDAC2, HDAC3, and HDAC6, respectively). Chronic treatment of Tg2576 mice with CM-414 dimini

AZD1446 HCl, also known as TC-6683, is a novel highly selective α4β2 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders. AZD1446 HCl showed favorable pharmaceutical properties and in vivo efficacy in animal models has been identified as a potential treatment for cognitive deficits associated with psychiatric or neurological conditions and had been evaluated in phase 2 clinical trials as a treatment for Alzheimer's disease.

AZD1446 tosylate, also known as TC-6683, is a novel highly selective α4β2 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders. AZD1446 tosylate showed favorable pharmaceutical properties and in vivo efficacy in animal models has been identified as a potential treatment for cognitive deficits associated with psychiatric or neurological conditions and had been evaluated in phase 2 clinical trials as a treatment for Alzheimer's disease.

Cemdomespib (KU-596) is a potent second-generation Hsp90 modulator. cemdomespib induces a heat shock response, induces Hsp70 levels and has neuroprotective effects. cemdomespib has been shown to improve sensory deficits in models of diabetic peripheral neuropathy.

Yonkenafil (Tunodafil), a novel phosphodiesterase 5 (PDE5) inhibitor, effectively reduces cerebral infarction, neurological deficits, edema, and neuronal damage in the infarcted area. It potentially enhances cognitive function through neurogenesis modulation and may have therapeutic effects on Alzheimer's disease.

Apicidin (OSI 2040) is a histone deacetylase (HDAC) inhibitor with antiparasitic activity and antiproliferative activity.Apicidin attenuates memory deficits, inhibits cell growth and proliferation, and induces apoptosis and autophagy by decreasing Abeta load in APP/PS1 mice, and can be used to study leukemia.

Desethoxy quetiapine, an active metabolite of the atypical antipsychotic quetiapine, primarily forms through the action of the cytochrome P450 (CYP) isoform CYP3A5. This compound binds to dopamine D2 receptors with an IC50 value of 1,330 nM. In vivo, desethoxy quetiapine at dosages of 20 and 40 mg/kg mitigates dopamine receptor agonist apomorphine-induced climbing behavior and ameliorates swimming deficits in mice, showcasing its potential modulatory effects on dopamine-mediated behaviors.

2-Amino-4-(2-aminophenyl)-4-oxobutanoic acid is a ketone and amino acid derivative with a variety of biological functions including vasodilatory, immunomodulatory, and neuromodulatory activities.2-Amino-4-(2-aminophenyl)-4-oxobutanoic acid is the precursor of niacin. 2-Amino-4-(2-aminophenyl)-4-oxobutanoic acid is the precursor of nicotinic acid. Abnormal production of 2-Amino-4-(2-aminophenyl)-4-oxobutanoic acid has been linked to cognitive deficits and depressive symptoms associated with neurological disorders. 2-Amino-4-(2-aminophenyl)-4-oxobutanoic acid is overexpressed in certain types of cancer cells and may be used to assess cancer risk. Expressed and may be used as a biomarker for assessing cancer risk.

The compound 4A7C-301-Nurr1 agonist is a specific agonist for the nuclear receptor-related 1 (Nurr1). By binding to the Nurr1 ligand-binding domain with an IC50 value of 48.22 nM, it enhances the transcriptional activity of both Nurr1-LBD and the full-length Nurr1, as demonstrated in reporter assays using SK-N-BE(2)C human neuroblastoma cells, with EC50 values of 6.53 and 50-70 µM, respectively. Additionally, administration of 4A7C-301-Nurr1 agonist at a dosage of 5 mg/kg per day has been shown to mitigate dopaminergic cell death in the striatum and substantia nigra pars compacta and ameliorate motor and olfactory deficits in mouse models of Parkinson's disease, circumventing the induction of dyskinesia-like behaviors. These models were induced either by the neurotoxin MPTP or by overexpression of α-synuclein.

1-Linoleoyl lysophosphatidic acid (1-linoleoyl LPA), a glycerophospholipid with linoleic acid at its sn-1 position, acts as an LPA2 receptor agonist and is the predominant LPA form in both mouse and human plasma. This compound preferentially boosts intracellular calcium in Sf9 cells expressing the LPA2 receptor (EC50 = ~10 nM), compared to those with LPA1 and LPA3 receptors (EC50s = ~200 and ~80 nM, respectively). Notably, 1-linoleoyl LPA serum concentrations are elevated in mice with NCTC clone 2472 tumors, while its plasma levels are reduced in primary progressive multiple sclerosis patients—unlike in those with relapsing-remitting multiple sclerosis—and inversely associate with the severity of neurological deficits.

Nevadistinel (NYX-458; NYX-3054) is a positive allosteric modulator of the N-methyl-D-aspartate (NMDA) receptor, indicated for mitigating cognitive deficits related to neurodegenerative conditions, including mild cognitive impairment, mild Alzheimer's disease, Parkinson's disease, and Lewy body disease [1].

MPT0G211 mesylate is a powerful and selective HDAC6 inhibitor (IC50 = 0.291 nM), with high oral bioavailability. It exhibits remarkable selectivity for HDAC6 over other HDAC isoforms (>1000-fold selectivity). Additionally, MPT0G211 mesylate can effectively cross the blood-brain barrier. In preclinical studies using an Alzheimer's disease model, MPT0G211 mesylate has shown promising results in reducing tau phosphorylation and cognitive deficits. Furthermore, this compound exhibits anti-metastatic and neuroprotective effects, making it a potential candidate for anticancer interventions. [1] [2] [3].

Eptastigmine, a potent and long-lasting cholinesterase inhibitor on age-related memory deficits.

p-fin4 is a peptide inhibitor targeting the interaction between STEP Phosphatase and GluA2 AMPA receptor, exhibiting a Ki of 0.4 μM. This compound has been shown to reverse memory deficits and exert anxiolytic and antidepressant effects in scopolamine-treated rats, suggesting its potential as a lead compound for developing novel cognitive enhancers and behavioral modulators [1].

ML-193 (CID 1261822) is a potent and selective GPR55 antagonist( IC50 : 221 nM). It shows more than 27-fold selectivity for GPR55 over GPR35, CB1 and CB2, and can improve the motor and the sensorimotor deficits of Parkinson’s disease (PD) rats.

Perospirone (Lullan) is an antagonist of serotonin 5HT2A receptors and dopamine D2 receptors. It also displays affinity towards 5HT1A receptors as a partial agonist.

Risevistinel (NYX-783), a positive allosteric modulator of the N-methyl-D-aspartate (NMDA) receptor, may mitigate cognitive deficits in neurodegenerative conditions, including mild cognitive impairment, mild Alzheimer's disease, Parkinson's disease, and Lewy body disease [1].

BChE/HDAC6-IN-1 is a dual BChE/HDAC6 inhibitor that exhibits potent and selective inhibition with IC50 values of 4 nM for BChE and 8.9 nM for HDAC6. It demonstrates efficacy in alleviating cognitive deficits in an Aβ1–42-induced mouse model, indicating its potential utility in Alzheimer's disease research [1].

Pozanicline reverses nicotine withdrawal-induced cognitive deficits, may be an effective component of novel therapeutic strategies for nicotine addiction. Pozanicline selectively activate neuronal nicotinic acetylcholine receptor (nAChR) subtypes, is a no

SEN-1269 is an amyloid-β (AB) aggregation inhibitor that acts by blocking Aβ(1-42) aggregation and protecting neuronal cell lines exposed to Aβ(1-42), reducing Aβ oligomer-induced LTP and memory deficits in vivo.

Brexpiprazole (OPC-34712) is a partial agonist of human 5-hydroxytryptamine (5-HT) 5-HT1A and dopamine D2 receptors.

ZSET1446 (ST-101) is a T-type calcium channel activator potentially for the treatment of learning deficits in various types of Alzheimer disease (AD) models.

Piromelatine is an agonist of melatonin MT1/MT2 receptors, 5-HT1A and 5-HT1D, and an antagonist of 5-HT2B.Piromelatine has antinociceptive activity with inhibitory effects on P2X3, TRPV1, and Nav1.7 channels, and can be used in studies of sleep-promoting, pain-relieving, anti-neurodegenerative, and antidepressant diseases. diseases, and can be used to improve memory deficits associated with chronic mild stress-induced lack of pleasure in rats.

KT109 is a selective inhibitor of DAGLβ (IC50 = 42 nM). KT109-treated wild-type mice displayed reductions in LPS-induced allodyni as well as in DAGL-β (-/-) micea. Repeated KT109 administration prevented the expression of LPS-induced allodynia, without ev

GSK-1034702 is an M1 mAChR agonist that improves cognitive deficits and may be useful in the study of neurologic disorders.

VU6004909 is a positive allosteric modulator of the mGlu5 receptor (pEC50: 7.59), exhibiting antipsychotic-like effects. It has the capability to reverse MK801-induced cortical hyperactivity and cognitive deficits [1] [2].

Guanfacine is a selective agonist of the α2A receptor.

Guanfacine hydrochloride (Intuniv) is a centrally acting antihypertensive agent with specificity towards ADRENERGIC ALPHA-2 RECEPTORS.