Nervous System Disease Models

Dizocilpine maleate (MK-801 maleate) is a potent, selective and non-competitive NMDA receptor antagonist with K_d of 37.2 nM in rat brain membranes.

Okadaic acid, a marine toxin, is an inhibitor of protein phosphatases (PP). Okadaic acid has a significantly higher affinity for PP2A (IC₅₀=0.1-0.3 nM), and inhibits PP1 (IC₅₀=15-50 nM), PP3 (IC₅₀=3.7-4 nM), PP4 (IC₅₀=0.1 nM), PP5 (IC₅₀=3.5 nM), but does not inhibit PP2C. Okadaic acid increases of phosphorylation of a number of proteins by inhibiting PP, and acts a tumor promoter. Okadaic acid induces tau phosphorylation.

Dizocilpine (MK-801), a potent anticonvulsant, is a selective and non-competitive NMDA receptor antagonist, with a K_d of 37.2 nM in rat brain membranes. Dizocilpine acts by binding to a site located within the NMDA associated ion channel and thus prevents Ca²⁺ flux.

β-Amyloid (1-42) (Amyloid β-peptide (1-42), human TFA, a 42-amino acid peptide that has not been treated with HFIP, is a brain-penetrant amyloid protein fragment, which can be used in research on Alzheimer's disease and Down’s syndrome. β-Amyloid (1-42), human TFA remaining as a monomer exhibits antioxidant and neuroprotective effects. β-Amyloid (1-42), human TFA, after being monomericized by HFIP and dissolved in DMSO to form the stock solution, on the one hand, can form soluble oligomers (AβOs) when incubated at 4 °C, which have synaptic toxicity and neurotoxicity; on the other hand, it can be incubated at 37 °C to form insoluble fibrils, with lower neurotoxicity, and participating in the oxidative damage process. Aβ42 oligomers bind to various neuronal surface receptors (such as PrPc, mGluR5, NMDA receptors, etc.), triggering oxidative stress, calcium homeostasis imbalance, and synaptic toxicity via activating downstream signaling pathways, leading to neuronal dysfunction and death.

β-Amyloid (1-42), human, HFIP-treated, a 42-amino acid peptide that has been treated with HFIP from β-Amyloid (1-42), human (HY-P1363A), is a brain-penetrant amyloid protein fragment, which can be used in research on Alzheimer's disease and Down’s syndrome. β-Amyloid (1-42), human, HFIP-treated remaining as a monomer exhibits antioxidant and neuroprotective effects. β-Amyloid (1-42), human, HFIP-treated, after being dissolved in DMSO to form the stock solution, on the one hand, can form soluble oligomers (AβOs) when incubated at 4°C, which have synaptic toxicity and neurotoxicity; on the other hand, it can be incubated at 37°C to form insoluble fibrils, with lower neurotoxicity, and participating in the oxidative damage process. Aβ42 oligomers bind to various neuronal surface receptors (such as PrPc, mGluR5, NMDA receptors, etc.), triggering oxidative stress, calcium homeostasis imbalance, and synaptic toxicity via activating downstream signaling pathways, leading to neuronal dysfunction and death.

Endothelin 1 (swine, human) (ET-1) is a synthetic peptide with the sequence of human and swine Endothelin 1, which is a potent endogenous vasoconstrictor. Endothelin 1 acts through two types of receptors ET_A and ET_B.

Pilocarpine is an orally active, selective M3 muscarinic acetylcholine receptor agonist. Pilocarpine can induce seizures. Pilocarpine is used in research on conditions such as epilepsy, dry mouth (xerostomia), and elevated intraocular pressure.

AY 9944 is a specific cholesterol biosynthesis inhibitor. AY 9944 inhibits the 7-dehydro cholesterol Δ7-reductase (DHCR7) enzyme with an IC₅₀ of 13 nM. AY 9944 causes hypocholesterolemia and accumulation of 7DHC. At high doses, AY 9944 inhibits also in cultured embryos sterol Δ7-Δ8 isomerase, which causes the accumulation of cholest-8-en-3β-ol.

Quinolinic acid, an endogenous metabolite of tryptophan, is a N-methyl-D-aspartate receptor (NMDA receptor) agonist. Quinolinic acid increases glutamate efflux, induces the generation of ROS, activates nitric oxide synthase, produces excessive NO, leading to calcium ion influx and neuronal apoptosis.

Haloperidol is a potent dopamine D2 receptor antagonist, widely used as an antipsychotic agent. Haloperidol can be used in the study of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal.

Fenclonine is a selective and irreversible tryptophan hydroxylase inhibitor, which is a rate-limiting enzyme in the biosynthesis of serotonin. Fenclonine can be used in carcinoid syndrome research.

Reserpine is an inhibitor of the vesicular monoamine transporter 2 (VMAT2).

5-Hydroxytryptophan, a tryptophan metabolite, is a direct 5-hydroxytryptamine (5-HT) precursor and an L-aromatic amino acid decarboxylase substrate. .

β-Amyloid (1-42), (rat/mouse) is a 42-aa peptide, shows cytotoxic effect on acute hippocampal slices, and used in the research of Alzheimer's disease.

Lactacystin is a potent, orally active, irreversible, cell-permeable, selective 20S proteasome inhibitor (IC₅₀ = 4.8 μM). Lactacystin also inhibits the lysosomal enzyme cathepsin A. Lactacystin inhibits cell growth and induces apoptosisand cell cycle arrest, and has antiviral and antioxidative activity. Lactacystin induces neurite outgrowth and hypertension. Lactacystin has the potential for the research of cancer, Neurological Disease, hypertension and Malaria, and so on^{[2] [6]} .

Pexidartinib hydrochloride (PLX-3397 hydrochloride) is a potent, orally active, selective, and ATP-competitive colony stimulating factor 1 receptor (CSF1R or M-CSFR) and c-Kit inhibitor, with IC₅₀s of 20 and 10 nM, respectively. Pexidartinib hydrochloride exhibits 10- to 100-fold selectivity for c-Kit and CSF1R over other related kinases. Pexidartinib hydrochloride induces cell apoptosis and has anti-cancer activity.

3-Nitropropanoic acid (β-Nitropropionic acid) is an irreversible and orally active inhibitor of succinate dehydrogenase. 3-Nitropropanoic acid exhibits potent antimycobacterial activity with a MIC value of 3.3 μM. 3-Nitropropanoic acid can induce cell apoptosis.

Cuprizone is a copper chelating agent that forms a deep blue copper ketone complex with copper (II). The copper ketone reaction can be used in colorimetric tests for the presence of trace copper. Cuprizone can be used to induce some schizophrenia-like behavior in mice. Cuprizone acts on copper enzymes, including SOD1, cytochrome oxidase, and DβH, thereby causing oxidative stress and increasing DA levels in certain brain regions such as the medial prefrontal cortex (PFC).

β-Amyloid (1-40) TFA is a primary protein in plaques found in the brains of patients with Alzheimer's disease.

L-5-Hydroxytryptophan (L-5-HTP), a naturally occurring amino acid and a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid, is the immediate precursor of the neurotransmitter serotonin and a reserpine antagonist. L-5-Hydroxytryptophan (L-5-HTP) is used to treat fibromyalgia, myoclonus, migraine, and cerebellar ataxia.