Istradefylline is a very potent, selective and orally active adenosine A2A receptor antagonist with Ki of 2.2 nM in experimental models of Parkinson's disease.
Cytidine-13C-1 is the 13C labeled Cytidine. Cytidine is a pyrimidine nucleoside and acts as a component of RNA. Cytidine is a precursor of uridine. Cytidine controls neuronal-glial glutamate cycling, affecting cerebral phospholipid metabolism, catecholami
Levetiracetam(UCB L059) is a novel anticonvulsant with antihyperalgesic efficacy in inflammatory pain.Target: Calcium ChannelLevetiracetam is used to control some types of seizures in patients with epilepsy. This medicine cannot cure epilepsy and will only work to control seizures for as long as you continue to use it. The exact mechanism for levetiracetam is unknown. However, the drug binds to a synaptic vesicle protein, SV2A, which is believed to impede nerve conduction across synapses [1].Levetiracetam (10-200 mg/kg), ibuprofen (12.5-100 mg/kg), celecoxib (3.75-30 mg/kg), paracetamol (50-200 mg/kg), caffeine (15-100 mg/kg), and 2-drug combinations of levetiracetam with analgesics/caffeine produced a significant, dose-dependent reduction of inflammatory hyperalgesia. Isobolographic analysis revealed that levetiracetam exerts a synergistic interaction with analgesics, with approximately 7-, 9-, and 11-fold reduction of doses of both drugs in combination of levetiracetam with paracetamol, celecoxib, and ibuprofen, respectively. Analysis of the log dose-response curves for levetiracetam (1-50 mg/kg) in the presence of caffeine (10 mg/kg) and levetiracetam applied alone also revealed a synergistic interaction. Levetiracetam's ED50 in the presence of caffeine was reduced approximately 11-fold [2].Clinical indications: Epilepsy; Social phobiaFDA Approved Date: November 2008Toxicity: depression; hallucinations; suicidal thoughts
6,2',4'-Trimethoxyflavone is a potent aryl hydrocarbon receptor (AHR) antagonist. 6,2',4'-Trimethoxyflavone represses AHR-mediated gene induction[1].
BRL-15572 2Hcl is a 5-HT1D receptor antagonist with pKi of 7.9, also shows a considerable affinity at 5-HT1A and 5-HT2B receptors, exhibiting 60-fold selectivity over 5-HT1B receptor. IC50 Value: 7.9(pKi)Target: 5-HT1D Receptorin vitro: BRL-15572 displays high affinity and selectivity for h5-HT1D receptors. BRL-15572 has 60-fold higher affinity for h5-HT1D than 5-HT1B receptors. BRL-15572 binds to h5-HT1B and h5-HT1D receptors with pKB of less than 6 and 7.1, respectively. BRL-15572 stimulates [35S]GTP γ S binding in both cell lines, with potencies that correlated with their receptor binding affinities in both h5-HT1B and h5-HT1D receptor expressing cell lines. BRL-15572 reveals receptor binding affinities for 5-HT1A, 5-HT1B, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6 and 5-HT7 with pKi of 7.7, 6.1, 5.2, 6.0, 6.6, 7.4, 6.2, 5.9 and 6.3, respectively. In the h5-HT1D cell line, both BRL-15572 (1 μM) shifts the 5-HT concentration response curve with pKB of 7.1, respectively. BRL-15572 does have moderately high affinity at human 5-HT1A and 5-HT2B receptors.in vivo: In diabetic pithed rats, administration of the selective 5-HT1D receptor antagonist BRL-15572 (2 mg/kg) does not modify the decreased HR induced by vagal electrical stimulation. The effects of L-694,247 (50 μg/kg), a selective agonist for non-rodent 5-HT1B and 5-HT1D receptors, on the vagally induced bradycardia are not apparent after pretreatment with BRL-15572.
Anisotropine methobromide is an orally active anticholinergic muscarinic antagonist. Anisotropine methobromide can inhibit gastric acid secretion and is used as an adjunct to peptic ulcers[1].
Lithium chloride hydrate, an orally active mood stabilizer, is a potent virus inhibitor and effective immunomodulatory agent. Lithium chloride hydrate has antidepressant activity by inhibiting GSK3β and promoting neurogenesis. Lithium chloride hydrate alleviates cognition dysfunction and the symptoms of acute mania and depression. Lithium chloride hydrate can also be used for research of virus infection and Alzheimer's disease[1][2][3].
TC-I 2014 (compound 5) is a potent Benzimidazole-containing transient receptor potential melastatin 8 (TRPM8) antagonist, with IC50 values of 0.8 nM, 3.0 nM and 4.4 nM for canine, human and rat channels respectively. TC-I 2014 exhibits antiallodynic properties in pain models[1].
Aripiprazole (OPC-14597) monohydrate, an atypical antipsychotic, is a potent and high-affinity dopamine D2 receptor partial agonist. Aripiprazole monohydrate is an inverse agonist at 5-HT2B and 5-HT2A receptors and displays partial agonist actions at 5-HT1A, 5-HT2C, D3, and D4 receptors. Aripiprazole monohydrate can be used for the research of schizophrenia and COVID19[1][2][3][4].
TIPP is a potent and selective δ-opioid antagonist with a Ki value of 1.22 nM[1].
GNE-9278 is a highly selective positive allosteric modulator of NMDAR that acts at the GluN1 transmembrane domain (TMD). GNE-9278 acts on activated NMDARs to increase peak current and agonist affinity[1].
UBP710 is a selective NMDA receptor modulator. UBP710 displays greater activity in potentiating GluN2B-containing receptors than those containing GluN2A[1].
Bilobalide is a biologically active terpenic trilactone present in Ginkgo biloba. An increasing number of studies have demonstrated its neuroprotective effects.IC50 Value: 3.33 (pIC50 Value) [1]Target: neuroprotectivein vitro: Inhibition by BB and GB was abolished in mutant receptors containing T6'S and S12'A substitutions, but their potencies were enhanced (42- and 125-fold, respectively) in S2'A mutant receptors [1]. BB enhanced the secretion of α-secretase-cleaved soluble amyloid precursor protein (sAPPα, a by-product of non-amyloidogenic processing of APP) and decreased the β amyloid protein (Aβ, a by-product of amyloidogenic processing of APP) via PI3K-dependent pathway [2].in vivo: Oral administration of bilobalide (10-30 mg/kg) significantly inhibited thermal hyperalgesia in response to carrageenan, capsaicin and paw incision, independent of dose, with an efficacy similar to that of diclofenac. In the carrageenan model, mechanical hypersensitivity and paw oedema were also significantly reduced after treatment with bilobalide (10-30 mg/kg) [3]. BB(4 and 8 mg/kg) significantly protected VD rats against cognitive deficits in the Morris water maze. Biochemical assessment showed that BB (4 and 8 mg/kg) increased superoxide dismutase (SOD) activity and glutathione (GSH) content, and decreased nitric oxide synthase (NOS) activity and malondialdehyde (MDA) content [4].Clinical trial: N/A
11-Oxo etiocholanolone (11-Ketoetiocholanolone) is a metabolite of Etiocholanolone. Etiocholanolone is the excreted metabolite of testosterone and has anticonvulsant activity[1][2].
Pizotifen malate is a potent 5-HT2 receptor antagonist, with a high affinity for 5-HT1C binding site.
β-Amyloid (35-25) is areverse version of β-Amyloid (25-35) (HY-P0128).
Myomodulin is a neuropeptide present in molluscs, insects, and gastropods.
BChE-IN-8 (compound 20) is an orally active, potent and BBB-penetrated BChE (butyrylcholinesterase) inhibitor, with IC50 values of 0.15 nM (eqBChE, equine serum BChE) and 45.2 nM (hBChE), respectively. High stability of BChE-IN-8 contributes to significantly improved blood concentration and tissue exposure. BChE-IN-8 can exert neuro-protecting and cognition improving properties through multiple modulations, including cholinergic system, Aβ aggregation, neuropeptide levels. BChE-IN-8 can be used for Alzheimer's disease (AD) research[1].
Atipamezole is a synthetic α2-adrenoceptor antagonist with a Ki of 1.6 nM.
Sesaminol, isolated from Justicia orbiculata, has antioxidative activity, Sesaminol inhibits lipid peroxidation and shows neuroprotection effect. Sesaminol potently inhibits MAPK cascades by preventing phosphorylation of JNK, p38 MAPKs, and caspase-3 but not ERK-MAPK expression[1][2][3][4].
Erigoster B is the active component of Erigeron breviscapus (Vant.) Hand.-Mazz. (an important Chinese herb), which has neuroprotective effects. Erigoster B can be used to prepare anti-nerve damage reagents to inhibit various nerve cell damage. It can also be used for cardio-cerebrovascular and tumor research[1][2][3].
P2X3 antagonist 37 is a potent P2X3 receptor antagonist with an IC50 of 32.45 nM for hP2X3 (WO2021115225A1, example 68)[1].
Adenosine-2'-monophosphate (2'-AMP) is converted by extracellular 2’,3'-CAMP. Adenosine-2'-monophosphate is further metabolized to extracellular adenosine (a mechanism called the extracellular 2’,3’-cAMP-adenosine pathway). Adenosine-2'-monophosphate inhibits LPS-induced TNF-α and CXCL10 production via A2A receptor activation[1][2].
ER176 is a next generation PET radioligand for imaging 18 kDa translocator protein (TSPO), a biomarker for neuroinflammation[1][2].
3-Bromocytisine (3-Br-cytisine) is a potent nACh receptors agonist, with IC50s are 0.28, 0.30 and 31.6 nM for hα4β4, hα4β2, and hα7-nACh, respectively. 3-Bromocytisine (3-Br-cytisine) shows different effects on high (HS) and low (LS) ACh sensitivity α4β2 nAChRs with EC50s are 8 and 50 nM, respectively[1][2].
Sulforhodamine 101 is a red fluorescent dye.
Tegaserod maleate is a partial agonist of the 5-HT4 receptor; stimulates the peristaltic reflex and accelerates gastrointestinal transit.IC50 value:Target: 5-HT4 agonistIn an in vivo model for peripheral nerve regeneration, mice receiving tegaserod at the site of injury showed enhanced recovery compared to control mice receiving vehicle control as evidenced by functional measurements and histology [1]. Treatment with fluoxetine (10 mg · kg(-1) · day(-1), days 36-42), tegaserod (1 mg · kg(-1) · day(-1), day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels [2]. Intravenous or intraduodenal tegaserod (0.3-1.0 mg.kg(-1)) had no inhibitory effect on mesenteric and colonic blood flow. Peroral treatment of rats with alosetron or tegaserod for 7 days did not modify mesenteric haemodynamics at baseline and after blockade of nitric oxide synthesis [3].
(D-Pro2,D-Trp6,8,Nle10)-Neurokinin B is a competitive antagonist of Neurokinin B (Neurokinin Receptor) with a pA2 of 5.5. (D-Pro2,D-Trp6,8,Nle10)-Neurokinin B shows no influence on Substance P or Neurokinin A[1].
FAAH-IN-5 (Compound 7) is a relative selective, irreversible fatty acid amide hydrolase (FAAH) inhibitor with an IC50 of 10.5 nM. FAAH-IN-5 shows low PAMPA (Parallel Artificial Membrane Permeability Assay) permeability[1].
Melanin Concentrating Hormone, salmon is a 19-amino-acid neuropeptide initially identified in the pituitary gland of teleost fish, which regulates food intake, energy balance, sleep state, and the cardiovascular system. Melanin-concentrating hormone is a ligand for an orphan G protein-coupled receptor (SLC-1/GPR24) and MCHR2.