Memantine, an amantadine derivative with some dopaminergic effects, has been proposed as an antiparkinson agent and has may be used to treat moderate to severe Alzheimer's disease. It acts on the glutamatergic system by blocking NMDA receptors.

Genipin ((+)-Genipin), an active aglycone derived from an iridoid glycoside called geniposide, is found in the fruit of Gardenia jasminoides Ellis.

CS-722 Free base is a synthetic central muscle relaxant with muscle relaxant activity and inhibitory effect on spinal reflex. CS-722 Free base may inhibit spontaneous inhibitory post-synaptic current and excitatory post-synaptic current in hippocampal culture by inhibiting sodium current and calcium current.

Galanin (1-16), mouse, porcine, rat is a hippocampal galanin receptor agonist(Kd = 3 nM) with high biological activity on locus coeruleus neurons.

3-MATIDA is an effective mGluR-1 antagonist (IC50: 6.3 μM, rat mGluR-1a). Displays ≥ 40-fold selectivity over other receptors: mGluR-5, mGluR-2, mGluR-4 (mGluR-4a) (IC50 > 300 μM), NMDA and GluR (AMPA) (IC50 = 250 μM). 3-MATIDA act as a neuroprotectant in cultured murine cortical cells and rat hippocampal slice cultures in vitro.

ZIP acetate is a novel, cell-permeable inhibitor of protein kinase Mζ (PKMζ), a constitutively active, atypical PKC isozyme involved in LTP maintenance. Selectively blocks PKMζ-induced synaptic potentiation in hippocampal slices in vitro. Reverses late-ph

Pep2m, myristoylated acetate is a Cell-permeable, myristoylated form of pep2m. Peptide inhibitor of the interaction between the C-terminus of the GluA2 (AMPA receptor) subunit and N-ethylmaleimide-sensitive fusion protein (NSF), a protein that regulates A

BMY-21502 is a potential cognitive enhancer that shows anti-hypoxia effects in the KCN-hypoxia model, delays the decay of hippocampal synaptic enhancement in vitro, and can be used to study Alzheimer's disease.

Nerolidol acetate is a natural sesquiterpene with anti-cancer, anti-inflammatory, antibacterial and anti-insect activities. Nerolidol acetate can inhibit parasite activity and inhibit schistosomiasis, nematodes, malaria, etc. Nerolidol acetate protects cells from oxidative damage to lipids, proteins and DNA, and has a protective effect on mouse hippocampal nerve cells.

KYL acetate is an EphA4 receptor tyrosine kinase inhibitor (Kd = 0.8 μM); inhibits EphA4-EphrinA5 interactions (IC50 = 6.34 μM). Prevents AβO induced synaptic damage, dendritic spine loss and prevents the blocking of LTP in hippocampal CA3-CA1 transmissions. Exhibits a long half life in cell culture media (8 and 12 hours in PC3 and C2C12 media respectively). Neuroprotective.

GGTI 2147 FA, a selective GGT inhibitor, abolishes bicuculline-induced increase in dendritic spine density in hippocampal experiments and may reduce learning and memory abilities in mice.

Lecozotan HCl (SRA-333) is a potent and selective 5-HT antagonist that significantly enhances KCl-stimulated glutamate and acetylcholine release from the hippocampal dentate gyrus and has cognitive enhancing properties. Chronic administration of Lecozotan HCl did not induce 5-HT(1A) receptor tolerance or desensitization in a behavioral model demonstrating 5-HT(1A) receptor function.

Suffruticosol A, a neuroprotective compound isolated from the seeds of P. lactiflora [1], mitigates scopolamine-induced neurodegenerative cellular damage and improves hippocampal cholinergic function. Additionally, it partially boosts BDNF signaling and has neuromodulatory effects, leading to the restoration of memory and cognitive performance in a scopolamine-induced mouse model.

Novel, cell-permeable inhibitor of protein kinase Mζ (PKMζ), a constitutively active, atypical PKC isozyme involved in LTP maintenance. Selectively blocks PKMζ-induced synaptic potentiation in hippocampal slices in vitro. Reverses late-phase LTP (IC50 = 1

KYL peptide is an EphA4 receptor tyrosine kinase inhibitor (Kd = 0.8 μM); inhibits EphA4-EphrinA5 interactions (IC50 = 6.34 μM). Prevents AβO induced synaptic damage, dendritic spine loss and prevents the blocking of LTP in hippocampal CA3-CA1 transmissions. Exhibits a long half life in cell culture media (8 and 12 hours in PC3 and C2C12 media respectively). Neuroprotective.

EM 163 is a TIR-TIR interaction inhibitor, which is a TIR (Toll/interleukin-1 receptor) structural domain mimic of the MyD88 protein. EM 163 targets the TIR structural domain in the IL-1 receptor and blocks the interaction with MyD88. EM 163 inhibits the production of inflammatory cytokines in vivo caused by staphylococcal enterotoxin B (SEB). EM 163 protects mice from SEB shock-induced death. In rat hippocampal neurons in vitro, EM 163 blocked the activation of p38 and the inhibitory effect of IL-1β on chemically induced long-term potentiation (LTP)-triggered protein synthesis.

Compound 3, 2,5-Dihydroxy-4-methoxyacetophenone, is isolated from the 80% methanol extract of the roots of Cynanchum paniculatum Kitagawa and has been shown to inhibit glutamate-induced cytotoxicity in the hippocampal HT22 cell line [1].

Tityustoxin-Kα (TsTx-Kα) acts as an inhibitor of potassium voltage-gated channels, exhibiting a dose-dependent blockade of the sustained outward current in cultured hippocampal neurons [1].

GluR23Y, a biologically active peptide, was utilized in an ELISA-based cell-surface assay to assess insulin-stimulated endocytosis of native AMPA receptors in cultured hippocampal neurons. GluR23Y effectively inhibited the insulin-induced decrease in receptor presence. The inhibition of insulin effects was achieved by introducing GluR23Y into neurons through fusion with the membrane transduction domain of HIV-1 TAT.

Betamethasone 21-phosphate is a synthetic glucocorticoid.1It prevents increases in macrophage and eosinophil numbers in bronchoalveolar lavage fluid (BALF) and decreases in blood leukocyte numbers in a guinea pig model of parainfluenza-3 viral infection when administered at a dose of 8 mg/kg but does not prevent airway hyperresponsiveness after infection.2Betamethasone 21-phosphate inhibits cell infiltration into the aqueous humor in a rat model of endotoxin-induced uveitis when administered topically or subcutaneously at doses of 0.01-1% or 1 mg/kg, respectively.3It increases maximal lung pressure volume curves in fetal sheep when administered to pregnant ewes at 0.75 gestation at doses of 80 and 170 μg/kg.1Betamethasone 21-phosphate increases body weight, impairs learning and memory, increases anxiolytic behavior, and reduces hippocampal neurogenesis in CD-1 mice but reduces body weight and increases neurogenesis with no effect on anxiety in high-anxiety DBA/2 mice when administered at a dose of approximately 25 mg/kg per day in the drinking water for seven weeks.4Formulations containing betamethasone 12-phosphate and betamethasone acetate have been used in the treatment of severe allergic conditions and a variety of immune-related conditions. 1.Loehle, M., Schwab, M., Kadner, S., et al.Dose-response effects of betamethasone on maturation of the fetal sheep lungAm. J. Obstet. Gynecol.202(2)186.e181-186.e187(2010) 2.Leusink-Muis, A., Ten Broeke, R., Folkerts, G., et al.Betamethasone prevents virus-induced airway inflammation but not airway hyperresponsiveness in guinea pigsClin. Exp. Allergy29(Suppl. 2)82-85(1999) 3.Tsuji, F., Sawa, K., Kato, M., et al.The effects of betamethasone derivatives on endotoxin-induced uveitis in ratExp. Eye Res.64(1)31-36(1997) 4.Aiello, R., Crupi, R., Leo, A., et al.Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesisBehav. Brain Res.278155-166(2015)

Prostaglandin D2 ethanolamide (PGD2-EA) is a bioactive lipid produced by the sequential metabolism of anandamide (arachidonoyl ethanolamide) by cyclooxygenase (COX) enzymes, in particular by COX-2, and PGD synthase. The biosynthesis of PGD2-EA from anandamide can also be increased when anandamide metabolism is diminished by deletion of fatty acid amide hydrolase. PGD2-EA is inactive against recombinant prostanoid receptors, including the D prostanoid receptor. It increases the frequency of miniature inhibitory postsynaptic currents in primary cultured hippocampal neurons, an effect which is the opposite of that induced by anandamide.. PGD2-EA also induces apoptosis in colorectal carcinoma cell lines.

Traxoprodil (CP101606) is a selective NMDA antagonist and protects hippocampal neurons (IC50: 10 nM).

L-803087 TFA is a highly potent and selective agonist of the somatostatin sst4 receptor, exhibiting a Ki value of 0.7 nM. It displays a remarkable selectivity, being over 280-fold more preferential for the sst4 receptor compared to other somatostatin receptors. Furthermore, L-803087 TFA promotes AMPA-mediated synaptic responses in hippocampal preparations and enhances kainate-induced seizures in mice.

GluN1 (356-385) is an antigenic peptide implicated in N-methyl-D-aspartate receptor (NMDAR) encephalitis and has been shown to decrease the density of NMDAR surface clusters in hippocampal neurons. It serves as a tool to investigate the pathogenesis of anti-NMDAR encephalitis [1].

Amyloid (1-42), rat is a polypeptide composed of 42 amino acids. It is toxic to hippocampal slices and can be used in the study of alzheimer's disease.

Aflatrem is a tremorgenic mycotoxin with acute neurotoxic effects, a single low dose of aflatrem is able to induce degeneration of neuronal processes in hippocampal neurotransmitter systems. Aflatrem potentiates the gamma-aminobutyric acid (GABA)-induced

Cell-permeable, myristoylated form of pep2m. Peptide inhibitor of the interaction between the C-terminus of the GluA2 (AMPA receptor) subunit and N-ethylmaleimide-sensitive fusion protein (NSF), a protein that regulates AMPA receptor function. Reduces pos

Negative control for st-Ht31 . Gorshkov et al (2017) AKAP-mediated feedback control of cAMP gradients in developing hippocampal neurons. Nat.Chem.Biol. 13 425 PMID:28192412 |Vijayaraghavan et al (1997) Protein kinase A-anchoring inhibitor peptides arrest mammalian sperm motility. J.Biol.Chem. 272 4747 PMID:9030527 |Vincent et al (2017) Signaling: Spatial regulation of axonal cAMP. Nat.Chem.Biol. 13 348 PMID:28328917

VU-29 is a positive allosteric mGlu5 receptor modulator with EC50=9 nM and Ki=244 nM for rmGluR5. It is selective for mGluR5 relative to other mGluR subtypes (EC50: rmGluR1/rmGluR2=557 nM/1.5 μM; hmGluR4=154 nM).

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)

8-hydroxy Efavirenz is a major oxidative metabolite of the non-nucleoside reverse transcriptase inhibitor efavirenz . 8-hydroxy Efavirenz is formed when efavirenz is metabolized by the cytochrome P450 (CYP) isoform CYP2B6. It induces apoptosis in rat primary hippocampal neurons and loss of dendritic spines in rat primary hippocampal neuronal cultures when used at a concentration of 0.01 μM.

Potent somatostatin receptor 1 (sst1) agonist; displays selectivity for sst1 (IC50 values are 30.9 nM, 345 nM, > 1 μM, > 10 μM and > 10μM for human sst1, sst3, sst4, sst2 and sst5 respectively). Attenuates somatostatin release in the rat nucleus accumbens

AK-1 is a sirtuin 2 (SIRT2) inhibitor (IC50:12.5 µM).that prevents hippocampal neurodegeneration in Alzheimer's disease models and induces cell cycle arrest in colon carcinoma cells.

L-Albizziin (2-Methoxyidazoxan monohydrochloride) is a highly potent selective antagonist of the alpha 2r adrenergic receptor, with little or no antagonistic effect on imidazoline. It has a significantly higher affinity for the alpha 2D adrenergic receptor (pKd9.7) in guinea pigs than for the alpha 2A adrenergic receptor (pKd8.2) in rabbits.

Tat-CBD3 is a chemical compound inhibiting the interaction between the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2), as well as the interaction between CRMP2 and the NMDA receptor NR2B subunit. At a concentration of 10 µM, Tat-CBD3 reduces the Cav2.2-CRMP2 interaction by 43% in cell-free assays and impedes the NMDA receptor NR2B subunit-CRMP2 interaction in immunoprecipitation assays. It lowers voltage-induced calcium currents by about 60% in primary rat dorsal root ganglion (DRG) neurons and decreases glutamate-induced cytosolic calcium level rises in primary rat hippocampal neurons. When administered at 20 mg/kg, Tat-CBD3 lessens infarct volume in a rat model of cerebral ischemia following middle cerebral artery occlusion (MCAO). Additionally, intrathecal delivery of Tat-CBD3 at a dose of 20 µg/5 µl mitigates carrageenan-induced thermal hypersensitivity in rats.

RC363 is an inhibitor of ferroptosis and a derivative of the antioxidant and hypocholesterolemic agent probucol .1It reduces 2,2-diphenyl-1-picrylhydrazyl radicals by approximately 40% in a cell-free assay when used at a concentration of 25 μM. RC363 prevents glutamate-induced toxicity in HT22 cultured hippocampal cells (IC50= 234.5 nM) but does not reduce oxidant levels in these cells. It increases the levels of glutathione peroxidase 1 (GPX1) and the activity of GPX in glutamate-challenged HT22 cells when used at a concentration of 3 μM. RC363 inhibits ferroptosis induced by the GPX4 inhibitor RSL3 in HT22 cells (IC50= 173.6 nM). 1.Bueno, D.C., Canto, R.F.S., de Souza, V., et al.New probucol analogues inhibit ferroptosis, improve mitochondrial parameters, and induce glutathione peroxidase in HT22 cellsMol. Neurobiol.57(8)3273-3290(2020)

Tamapin TFA, a venom peptide isolated from the Indian red scorpion (Mesobuthus tamulus) [1], selectively targets and blocks small conductance Ca(2+)-activated K(+) (SK) channels, particularly the SK2 subtype (Potassium Channel). It is known to inhibit SK channel-mediated currents in the hippocampal pyramidal neurons.

In the CA3 hippocampal region, Palmitone against pentylenetetrazole-caused neuronal damage.

Morachalcone A displays significant tyrosinase inhibitory activity (IC50, 0.013 uM); it also exerts strong pancreatic lipase inhibition with IC 50 value of 6.2 uM. Morachalcone A exhibits neuroprotective effects on HT22-immortalized hippocampal cells agai

BRL 44408 Maleate Salt is a selective α2A-adrenoceptor antagonist with Ki value of 1.7 nM. BRL 44408 Maleate Salt increases the release of hippocampal noradrenalin following systemic administration.

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

TP-050 is a potent, selective NMDAR agonist that is orally active, showing EC50 values of 0.51 µM for GluN2A and 9.6 µM for GluN2D. This compound can cross the blood-brain barrier (BBB), enhancing hippocampal long-term (LTP) potentiation and neuronal signal transmission.

Afizagabar (S44819) is a first-in-class, competitive, and selective antagonist at the GABA-binding site of the α5-GABAAR, with an IC50 of 585 nM for α5β2γ2 and a Ki of 66 nM for α5β3γ2. Afizagabar enhances hippocampal synaptic plasticity and exhibits pro-cognitive efficacy[1]. Afizagabar (S44819) is a competitive α5-GABAAR antagonist (Kb=221 nM). Afizagabar selectively inhibits extrasynaptic α5-GABAARs of mouse CA1 pyramidal neurons[1]. Afizagabar (1 and 3 mg/kg; i.p.) significantly diminishes the marked increase in total errors induced by Scopolamine[1]. [1]. Etherington LA, et al. Selective inhibition of extra-synaptic α5-GABAA receptors by S44819, a new therapeutic agent. Neuropharmacology. 2017;125:353-364.

Biotin-amyloid-β (1-42) peptide is an affinity probe that allows amyloid-β (1-42) (Aβ42) to be detected or immobilized through interaction with the biotin ligand. It has been used to identify Aβ42 interaction partners in rat hippocampal synaptosomal membranes.

Lei-Dab7 TFA, a selective and high-affinity blocker of the K Ca 2.2 (SK2) channel with a dissociation constant (K d) of 3.8 nM, demonstrates over 200-fold selectivity for K Ca 2.2 compared to K Ca 2.1, K Ca 2.3, K Ca 3.1, K v, and Kir2.1. Furthermore, Lei-Dab7 TFA enhances theta-burst responses and long-term potentiation (LTP) in rat hippocampal slices in vitro.

4′-Demethylnobiletin, a bioactive metabolite, activates the PKA/ERK/CREB signaling pathway, enhances CRE-mediated transcription in hippocampal neurons, and reverses memory impairment linked to NMDA receptor antagonism through ERK signaling stimulation [1].

FK962 is an enhancer of somatostatin release, which exerts cognitive-enhancing actions in rats. FK960 increases synaptic density in the hippocampal CA3 region of aged rats.

Nrf2-ARE/hMAO-B/QR2 modulator 1 is a new resveratrol-based multitarget-directed ligands (MTDLs) that showed a well-balanced MTDL profile: cellular activation of the NRF2-ARE pathway (CD = 9.83 μM), selective inhibition of both hMAO-B and QR2 (IC50s = 8.05 and 0.57 μM), and the best ability to promote hippocampal neurogenesis. Nrf2-ARE/hMAO-B/QR2 modulator 1 exerts neuroprotective and antioxidant actions in both acute and chronic Alzheimer models using hippocampal tissues.

GAT229 is a positive allosteric modulator of cannabinoid receptor 1 (CB1) and the S-(-) enantiomer of the CB1 modulator GAT211. It does not activate the receptor on its own but enhances the binding and activity of CB agonists. GAT229 (1 μM) enhances the binding of the CB1 full agonist CP 55,940 to CHO cells expressing human recombinant CB1 (hCB1), as well as the activity of 2-arachidonoyl glycerol , arachidonoyl ethanolamide , and CP 55,940 in arrestin2 recruitment assays and increases ERK1/2 and PLCβ3 phosphorylation in HEK293 cells expressing hCB1. GAT229 (1 μM) enhances depolarization-induced suppression of excitation but does not inhibit excitatory postsynaptic currents (EPSCs) in murine autaptic hippocampal neurons. GAT229 (0.2%, topical) reduces intraocular pressure by 5.8 and 7.7 mm Hg after 6 and 12 hours, respectively, in a transgenic mouse model of ocular hypertension using nose, ear, eye mutation (nee) mice.

Potent and selective β-secretase (BACE) inhibitor (IC50 values are 10.2 and 20.3 nM for human BACE2 and BACE1, respectively). Displays >5,000-fold selectivity for BACE over other proteases including cathepsin D, pepsin and renin. Inhibits Aβ1-40 and Aβ1-42 production in cells expressing mutated APP. Reduces hippocampal and cortical Aβ and sAPPβ levels in an Alzheimer's disease mouse model.