neurotoxicity

Ferrostatin-1 (Fer-1) is a potent and selective inhibitor of ferroptosis. Ferrostatin-1 potently inhibits Erastin-induced ferroptosis in HT-1080 cells with an EC50 of 60 nM. Ferrostatin-1 also exhibits antioxidant and antifungal activities.

Benzamide (Amid kyseliny benzoove), an inhibitor of poly(ADP-ribose) polymerase, is a derivative of benzoic acid.

Tetrahydropapaverine hydrochloride (Norlaudanosine HCl) , an analogue of salsolinol and tetrahydropapaveroline, has neurotoxicity on dopamine neurons.

Idebenone (CV-2619) is a synthetic analogue of ubiquinone (Coenzyme Q10), a vital cell antioxidant and essential component of the Electron Transport Chain (ETC).

Erbulozole (R 55104) is a potent synthetic microtubule inhibitor with anti-invasive, anti-tumor, and radiosensitizing activities that induces Wernicke's encephalopathy-like neurotoxicity.

Orphenadrine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that inhibits clonal HERG channels in a concentration-dependent manner, producing an IC of 0.85 μM in HEK cells.Orphenadrine is an antagonist of central and peripheral muscarinic receptors. Attenuation is blocked by mutations in pore residues Y652 or F656. Orphenadrine has antispasmodic, analgesic, and anticholinergic activity and protects against glutamatergic neurotoxicity in vitro and in vivo.Orphenadrine has inhibitory effects on sodium channels and can be used in the treatment of Parkinson's disease.

Davunetide acetate is derived from activity-dependent neuroprotective protein existing in the mammalian CNS. Davunetide acetate is a microtubule-stabilizing peptide and inhibits Aβ aggregation and Aβ-induced neurotoxicity. Davunetide acetate possesses neuroprotective, neurotrophic, and cognitive protective properties.

S1R agonist 2 is a selective S1R agonist with a Ki of 88 nM for S2R and 1.1 nM for S1R and is protective against ROS and NMDA-induced neurotoxicity.

DB04760 is a highly selective, non-zinc-chelating inhibitor of MMP-13 (IC50: 8 nM). DB04760 obviously decreases paclitaxel neurotoxicity and has anticancer activity.

Copper histidine inhibited Ctr1-mediated cellular uptake of oxaliplatin in vitro without altering oxaliplatin accumulation of platinum or neurotoxicity in DRG tissues in vivo. Copper histidine is administered orally for the treatment of Menkes disease.

Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride) is an neurotransmitter dopamine antagonist.

1. Linarin (Acacetin-7-O-rutinoside) (acacetin-7-O-β-d-rutinoside) shows selective dose dependent inhibitory effect on acetylcholinesterase. 2. Linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways. 3. Linarin prevents A beta-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3b and up-regulates Bcl-2. 4. The piperine significantly enhanced the oral absorption of Linarin in rats by inhibiting P-glycoprotein mediated cellular efflux during the intestinal absorption and likely simultaneously by inhibiting the metabolism of Linarin.

Oxidopamine hydrobromide (6-OHDA hydrobromide) is a neurotransmitter dopamine antagonist.

AM 281, a cannabinoid antagonist, reduces neurologic dysfunction and mortality rate after cecal ligation and puncture in rats.

Hibifolin is a flavonol glycoside natural product,is a potential inhibitor of adenosine deaminase (Ki of 49.92 μM). Hibifolin protects neurons against beta-amyloid-induced neurotoxicity.

Biapenem (CLI 86815) is a 1-beta-methylcarbapenem antibiotic with a wide range of antibacterial activity. Biapenem has similar antibacterial activity to that of imipenem, but is more stable against human renal dehydropeptidase-I and with less neurotoxicity.

Indibulin (D 24851) is a synthetic small molecule with antimitotic and potential antineoplastic activities.Indibulin an orally applicable inhibitor of tubulin assembly, shows potent anticancer activity with a minimal neurotoxicity. Indibulin reduces inter-kinetochoric tension, produces aberrant spindles, activates mitotic checkpoint proteins Mad2 and BubR1, and induces mitotic arrest and apoptosis.

1. Talatisamine (12 μM) and TEA (5mM) inhibits the enhanced I(K) caused by Aβ4 oligomers, attenuates cytotoxicity of Aβ oligomers by restoring cell viability and suppressing K(+) loss related apoptotic response. 2. Talatisamine can therefore be considered

Notoginsenoside R2 (20(S)-Notoginsenoside R2) has neuroprotection against 6-OHDA-induced neurotoxicity, is associated with Notoginsenoside R2-mediated P90RSK and Nrf2 activation through MEK1/2-ERK1/2 pathways.

D-Arabitol is a polyol that can lead to neurotoxicity when accumulated in the body.

Tolmetin (Tolectin) is a Nonsteroidal Anti-inflammatory Drug. The mechanism of action of tolmetin is as a Cyclooxygenase Inhibitor. The chemical classification of tolmetin is Nonsteroidal Anti-inflammatory Compounds.

HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated inhibitor of HDAC6 (IC50 = 0.025 μM) that inhibits Aβ 1-42 self-aggregation and AChE with IC50 values of 3.0 and 0.72 μM, respectively. Additionally, HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

Neuronotoxicity-IN-1 is a pyridothiazine derivative. Neuronotoxicity-IN-1 is an inhibitor of kainic acid neurotoxicity with neuroprotective activity[1].

HDAC6-IN-6 (compound 6a) is a potent HDAC6 inhibitor with an IC50 value of 0.025 μM that can penetrate the BBB. It exhibits strong inhibitory activity against AChE and Aβ 1-42 self-aggregation with IC50 values of 0.72 and 3.0 μM, respectively. HDAC6-IN-6 also enhances neurite outgrowth without significant neurotoxicity [1].

(+)-Afzelechin has a neuroprotective effect on the glutamate-induced neurotoxicity in HT22 cells, it has ABTS cation radical scavenging effects with IC50 values of 23.7 microM

Setosusin is a meroterpenoid fungal metabolite originally isolated from C. setosus. It reduces neurotoxicity induced by amyloid-β (Aβ) aggregates in PC12 cells (EC50 = 112.6 μM). In vivo, setosusin (30 mg/kg) induces tremors in mice.

Peimisine 3-O-β-D-glucopyranoside (Compound 1), a steroid alkaloid isolated and purified from Fritillaria unibracteata, demonstrates a moderate protective effect against rotenone-induced neurotoxicity in the PC12 cell line [1].

BML-259 is an inhibitor of CDK5 and CDK2 with IC50s of 64 and 98 nM, respectively. BML-259 can be used in studies about the treatment of cancer and neurodegenerative diseases.

PQM130 is a neuroprotective compound ,and is a potential anti-AD drug.

D-Arabitol is a polyol that can lead to neurotoxicity when accumulated in the body.

αSyn-IN-576755 is a novel inhibitor of αSyn fibrillization, blocking fibril growth and suppressing A53T αSyn neurotoxicity.

2'-Acetylacteoside has antioxidative activity. It can significantly attenuate glutamate-induced neurotoxicity at concentrations ranging from 0.1 to 10 μM. 2'-Acetylacteoside shows antiproliferative effects on aortic smooth muscle, indicates that it may ha

GSK-3β inhibitor 15 (Compound 54), with an IC50 of 3.4 nM, effectively suppresses Aβ 1-42-induced phosphorylation of GSK-3β and tau protein, as well as LPS-induced iNOS expression, demonstrating neuroprotective properties against Aβ 1-42-induced neurotoxicity and indicating potential utility in Alzheimer's disease (AD) research [1].

Pinostrobin, a potent flavonoid inducer, exerts a neuroprotective effect against Aα²(25-35)-induced neurotoxicity in PC12 cells, at least in part, via inhibiting oxidative damage and calcium overload, as well as suppressing the mitochondrial pathway of ce

1-Aminocyclopropane-1-carboxylic acid (ACC) is an intermediate in the synthesis of ethylene, the plant hormone responsible for biological processes ranging from seed germination to organ senescence. It is a small molecule agonist at the glycine modulatory site of the NMDA receptor (EC50 = 0.7-0.9 μM) in the presence of low levels (1 μM) of glutamate and as a competitive antagonist at the glutamate-binding site on NMDA receptors (EC50 = 81.6 nM) with high levels (10 μM) of glutamate.2 This compound has been reported to protect against neuron cell death in vivo models of ischemia by enabling moderate levels of NMDA receptor activation and attenuating any excess NMDA receptor signaling that may lead to neurotoxicity.

CI-943 is a novel potential antipsychotic drug that does not bind to dopamine (DA) receptors and has some developmental neurotoxicity.

Dasycarpol(9beta-Hydroxyfraxinellone) shows significant neuroprotective activity against glutamate-induced neurotoxicity in primary cultures of rat cortical cells at a concentration of 0.1 microM. Dasycarpol also shows moderate inhibitory activity on lung

Dehydroheliobuphthalmin has significant neuroprotective activities against glutamate- induced neurotoxicity.

1. Rhynchophylline (Mitrinermine) can protect against ischemic damage, probably via regulating the Akt/mTOR pathway. 2. Rhynchophylline can protect against glutamate-induced neuronal death, can inhibit MA impairment in cultured neurons in vitro. 3. Rhynchophylline and isorhynchophylline have a non-competitive antagonistic effect on the NMDA-type ionotropic glutamate receptors, suggest that these alkaloids exert their protective action against ischemia-induced neuronal damage by preventing NMDA, muscarinic M1, and 5-HT2 receptors-mediated neurotoxicity during ischemia.

Paeonilactone B ((+)-Paeonilactone B), a monoterpenoid from Paeonilactone, has neuroprotective activity, inhibits oxidative stress, and suppresses H2O2-induced neurotoxicity in rat cortical cells.

NSC363998 (free base), an orally active compound, suppresses rCGG90-induced neurotoxicity and is utilized in researching neurodegenerative disorders, including Fragile X associated tremor/ataxia syndrome (FXTAS) [1].

Heishuixiecaoline A protects against neurotoxicity in PC12 cells.

GABAA receptor agent 7 (compound 5c) is a potent positive modulator of the GABAA receptor with anticonvulsant activity in vitro and in vivo, and low neurotoxicity, making it suitable for epilepsy research [1].

Fenobucarb, a widely employed carbamate insecticide, poses potential risks to the cardiovascular and cerebrovascular systems in animals[1][2]. It triggers developmental neurotoxicity in zebrafish by engaging pathways related to inflammation, oxidative stress, degeneration, and apoptosis.

Piperazine (2HCl) is gamma-aminobutyric acid (GABA) agonists and its major effects appear to be on the central nervous system. Piperazine was the anthelmintic with the greatest number of reports of toxicoses and suspected toxicoses in cats. Piperazine neurotoxicity in cats and dogs usually was manifested by muscle tremors, ataxia, and/or behavioral disturbances within 24 hours after estimated daily dose(s) between 20 and 110 mg/kg[1]. For di-substituted derivatives, ciprofloxacin was selected and hybrids were synthesized via substitution at piperazinyl-N4. The reaction of piperazinyl-NH of ciprofloxacin with selected drugs resulted in pronounced growth inhibition of standard as well as resistant bacterial strains[2]. The parent piperazine 6 was found to exhibit a reasonable activity toward the HeLa and MDA MB 231 tumor cell lines (IC50= 9.2 and 8.4 μΜ, respectively)[3]. Piperazine adipate (10 mM) causes mortality of A. galli and H. gallinae after a maximum of 30 min exposure, inhibits malate oxidation by 78%, and inhibits aldolase activity in both parasites. Piperazine adipate (10 mM) also inhibits cholinesterase activity by 96% in Ascaridia galli (A. galli) and 93% in Heterakis gallinae (H. gallinae). Piperazine adipate inhibits oxaloacetate reduction by 26% and 55% in A. galli and H. gallinae, resepctively[4].

Caprospinol inhibits β-Amyloid (Aβ) protein neurotoxicity.

Brandioside (2'-Acetylpoliumoside), a phenylpropanoid glycoside obtainable from Callicarpa dichotoma Raeuschel, Verbenaceae, has antioxidant activity, attenuates glutamate-induced neurotoxicity, and can be used in the study of diabetes mellitus.

Compound 8b hydrochloride, a selective S1R agonist, exhibits affinity with K i s of 1.1 nM for S1R and 88 nM for S2R. It demonstrates neuroprotective effects against ROS and NMDA-induced neurotoxicity [1].

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].

BChE-IN-17 (compound 6n) is a potent and selective inhibitor of butyrylcholinesterase (BChE), with half-maximal inhibitory concentrations (IC50s) of 10.5 nM for equine BChE (eqBChE) and 32.5 nM for human BChE (hBChE). It shows over 1000-fold greater selectivity for BChE compared to acetylcholinesterase (AChE), while exhibiting low neurotoxicity and moderate neuroprotective effects [1].