impairments

Escitalopram Oxalate ((S)-(+)Citalopram oxalate) is a selective serotonin (5-HT) reuptake inhibitor (SSRI) with Ki of 0.89 nM.

Escitalopram (Seroplex) is a furancarbonitrile that is one of the SEROTONIN UPTAKE INHIBITORS used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia in preference to tricyclic antidepressants, which aggravate this condition.

Galanthaminone ((-)-Narwedine) is a cholinesterase (AChE) inhibitor, is used for the treatment of mild to moderate Alzheimer's disease and various other memory impairments.

7-bromoindirubin-3'-oxime (7BIO) is a caspase independent nonapoptotic cell death inducer. 7BIO is an inhibitor of FLT3, DYRK1A, DYRK2, Aurora B and Aurora C kinases.

Brilaroxazine (RP5063) is a potent multimodal dopamine/5-HT modulator. Brilaroxazine is a partial agonist of dopamine D2, D3, and D4 receptors, 5-HT1A (Ki =1.5 nM) and 5-HT2A (Ki = 2.5 nM), and has antagonist activity 5-HT2B, and 5-HT7 receptors with Kis of 0.19 nM and 2.7 nM, respectively. Brilaroxazine can be used for research about cognitive impairments in neuropsychiatric and neurological diseases.

Oxiracetam (ISF2522), a cyclic derivative of gamma-aminobutyric acid (GABA), is utilized for the treatment of cognitive impairments.

HFI-419 is a potent inhibitor of insulin-regulated aminopeptidase (IRAP) with a K i value of 0.48 μM. It is utilized in research pertaining to cognitive and memory impairments, including Alzheimer's disease, brain trauma, and stroke [1].

Bay 60-7550 is a selective and potent PDE2 inhibitor (Ki: 3.8 nM) that exerts positive inotropic effects on rat heart by increasing PKA-mediated phosphorylation and can be used to ameliorate cognitive impairments and memory disorders.

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].

BChE-IN-4 is a highly potent inhibitor of the enzyme butyrylcholinesterase, capable of crossing the blood-brain barrier. It effectively reduces learning and memory impairments resulting from a deficiency in cholinergic activity in a mouse model. BChE-IN-4 holds promise for further investigation in the field of Alzheimer's disease research [1].

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].

Deacetylforskolin is a diterpene and a derivative of forskolin that has been found inC. forskohliiand has diverse biological activities.1,2,3,4It activates rat adipocyte adenylyl cyclase (IC50= 20 μM) and inhibits glucose transport in rat adipocyte plasma membranes.2Deactylforskolin (30-1,000 μg/kg) reduces blood pressure in spontaneously hypertensive rats.3It also attenuates hypercapnia-induced impairments in the passive avoidance response in mice.4 1.Gabetta, B., Zini, G., and Danieli, B.Minor Diterpenoids of Coleus forskohliiPhytochemistry28(3)859-862(1989) 2.Joost, H.G., Habberfield, A.D., Simpson, I.A., et al.Activation of adenylate cyclase and inhibition of glucose transport in rat adipocytes by forskolin analogues: structural determinants for distinct sites of actionMol. Pharmacol.33(4)449-453(1988) 3.Bhat, S.V., Dohadwalla, A.N., Bajwa, B.S., et al.The antihypertensive and positive inotropic diterpene forskolin: Effects of structural modifications on its activityJ. Med. Chem.26(4)486-492(1983) 4.McCulloch, A.J., Thomson, T.A., and Deacon, R.Hypoxic amnesia and its reversal with forskolinBiochem. Soc. Trans.17(1)212-213(1988)

AChE-IN-39 (Compound 7c), with an IC50 value of 0.058 μM, is an acetylcholinesterase (AChE) inhibitor known for its DPPH scavenging activity and potential to ameliorate cognitive impairments in an aluminum chloride (AlCl3)-induced amnesia animal model, suggesting its usefulness in Alzheimer's disease research [1].

KDS2010 is a potent, highly selective, and reversible MAO-B inhibitor which shows 12,500-fold selectivity over MAO-A. KDS2010 overcomes the disadvantages of the irreversible MAO-B inhibitor and significantly attenuates increased astrocytic GABA levels and astrogliosis, thereby enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice.

[(3R)-3-Hydroxydodecanoyl]-L-carnitine is an endogenous metabolite[1].

WLB-87848 is a selective, orally active σ1 receptor agonist that can cross the blood-brain barrier, with a Ki value of 9 nM. It alleviates memory recognition impairments.

α-Synuclein inhibitor 9 (Compound 20C) targets and binds to cavities within mature α-synuclein fibrils, diminishing their β-sheet content. It effectively inhibits the aggregation of A53T α-synuclein, exhibits neuroprotective properties, enhances brain functionality, and alleviates motor impairments. This compound is utilized in research related to Parkinson's disease (PD). [1]

AF267 is a M1 muscarinic agonist that works by restoring cognitive impairments.

QR-0217 is a potent inhibitor of both Aβ1-40 and α-synuclein aggregation, exhibiting an IC50 of 7.5 µM for Aβ1-40. Additionally, QR-0217 has been shown to alleviate memory impairments attributed to Aβ neurotoxicity [1].

Yhhu-3792 hydrochloride is a compound that bolsters the self-renewal capacity of neural stem cells (NSCs), catalyzes the Notch signaling pathway, and upregulates expression of Hes3 and Hes5. It augments the NSC pool, stimulates endogenous neurogenesis in the mouse hippocampal dentate gyrus (DG), and enhances mice's spatial and episodic memory skills. This compound shows promise for researching learning and memory impairments linked to DG dysfunction [1].

Monoamine OxidaseB inhibitor 5 (Compound 16d) is a reversible and selective inhibitor of monoamine oxidase B (hMAO-B), with an IC50 value of 67.3 nM and a Ki of 82.5 nM. It exhibits favorable pharmacokinetic properties and low toxicity in rat models. Additionally, this compound alleviates motor impairments in a Parkinson’s mouse model induced by MPTP, and it is characterized by its ability to penetrate the blood-brain barrier (BBB).

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.

Chrysanthellin A, the principal saponin-derived compound isolated from Chrysanthellum americanum extract, is utilized in the research of digestive impairments [1].

BChE-IN-13 (Compound 17c) is an orally active, potent, and selective inhibitor of Butyrylcholinesterase (BChE), exhibiting IC50 values of 0.22 μM and 0.016 μM for eqBChE and hBChE, respectively. BChE-IN-13 enhances memory and cognitive impairments, making it valuable for Alzheimer's disease (AD) research [1].

SAR502250 is a potent, selective, ATP-competitive, orally active, and brain-penetrant GSK3 inhibitor with a human GSK-3β IC50 value of 12 nM, exhibiting antidepressant-like activity and being researched for potential application in Alzheimer’s disease (AD) treatment.

GRL-8234 is a small-molecule BACE1 inhibitor that reverses memory impairments and age-related cognitive decline.

Basmisanil (RG1662) is a negative allosteric modulator inverse agonist of GABAAα5 receptors.Formulations containing basmisanil are in clinical trials for the treatment of cognitive impairments associated with Down syndrome.

AQW051 (VQW-765) is an orally active alpha-7 nicotinic acetylcholine receptor (α7-nAChR) specific activator that interacts with recombinant human α7-nAChR expression (pKD value 7.56). Alpha7-nachr is considered an attractive target for the treatment of cognitive impairments associated with neurological disorders, so VQW-051 is often used in studies of anxiety disorders and acute anxiety.

RO-275 (compound 29), recognized for its potency and selectivity, acts as an orally active HCN1 inhibitor, exhibiting IC 50 values of 0.046 µM for HCN1, 14.3 µM for HCN2, 4.6 µM for HCN3, and 13.9 µM for HCN4. Notably, RO-275 enhances working memory, suggesting its research utility for cognitive impairments associated with brain disorders [1] [2].

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.

Compound 8 (5-HT6R antagonist 1), a 5-HT6R antagonist (K i : 5 nM), not only demonstrates inhibition of platelet aggregation and excellent metabolic stability but also reverses MK-801-induced memory impairments in rats, suggesting its utility in Alzheimer's disease (AD) research [1].

DSR-141562 is a new compound that can be taken orally and has a specific ability to inhibit phosphodiesterase 1 (PDE1) in the brain. This compound exhibits a preference for inhibiting human PDE1B, with an IC50 value of 43.9 nM. It also shows moderate inhibition of human PDE1A (IC50 = 97.6 nM) and PDE1C (IC50 = 431.8 nM). DSR-141562 is particularly useful in the study of positive symptoms, negative symptoms, and cognitive impairments associated with schizophrenia.

PH-002, an inhibitor targeting the intramolecular domain interaction of apolipoprotein (apo) E4 in neuronal cells, additionally enhances mitochondrial motility and promotes neurite outgrowth, thereby countering related impairments.

Amyloid-β (1-8) is a wild-type control for the mutation-containing amyloid-β (1-8, A2V) peptide .

Amyloid-β (1-42) (Aβ42) is a neurotoxic 42-amino acid protein fragment found in amyloid plaques in postmortem cerebral cortex from patients with Alzheimer's disease.1,2,3Aggregation of Aβ42 results in the formation of neurotoxic fibrils or globular oligomers.1Aβ42 accumulates in the brain of many transgenic mouse models of Alzheimer's disease and, in many models, the onset of amyloid deposition positively correlates with deficits in spatial learning and memory.4 1.Wolfe, M.S.Therapeutic strategies for Alzheimer's diseaseNat. Rev. Drug Discov.1(11)859-866(2002) 2.Iwatsubo, T., Odaka, A., Suzuki, N., et al.Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)Neuron13(1)45-53(1994) 3.Hardy, J.A., and Higgins, G.A.Alzheimer's disease: The amyloid cascade hypothesisScience256(5054)184-185(1992) 4.Jankowsky, J.L., and Zheng, H.Practical considerations for choosing a mouse model of Alzheimer's diseaseMol. Neurodegener.12(1)89(2017)