CP-465022 Maleate is a potent, and selective noncompetitive AMPA receptor antagonist with anticonvulsant activity. CP-465022 is against Kainate-induced response with an IC50 of 25 nM in rat cortical neurons. CP-465022 provides a new tool to investigate the role of AMPA receptors in physiological and pathophysiological processes[1][2].
Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia.Target: SNRIMilnacipran (Ixel, Savella, Dalcipran, Toledomin) is a serotonin-norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia. It is not approved for the clinical treatment of major depressive disorder in the USA, but it is in other countries.Milnacipran inhibits the reuptake of serotonin and norepinephrine in an approximately 1:3 ratio, respectively; in practical use this means a relatively balanced action upon bothneurotransmitters. Increasing both neurotransmitters concentration simultaneously works synergistically to treat both depression and fibromyalgia. Milnacipran exerts no significant actions onH1, α1, D1, D2, and mACh receptors, as well as on benzodiazepine and opioid binding sites. Milnacipran is well absorbed after oral dosing and has a bioavailability of 85%. Meals do not have an influence on the rapidity and extent of absorption. Peak plasma concentrations are reached 2 hours after oral dosing. The elimination half-life of 8 hours is not increased by liver impairment and old age, but by significant renal disease. Milnacipran is conjugated to the inactive glucuronide and excreted in the urine as unchanged drug and conjugate. Only traces of active metabolites are found.
AChE/BuChE-IN-2 (Compound 5f) is an orally active AChE and BuChE inhibitor with IC50 values of 0.72 μM and 0.16 μM, respectively. AChE/BuChE-IN-2 shows a non-competitive inhibition with AChE and shows potent self-induced β-amyloid (Aβ) aggregation inhibition with an IC50 of 62.52 μM. AChE/BuChE-IN-2 can cross the BBB[1].
Pramipexole 2Hcl is a partial/full D2S, D2L, D3, D4 receptor agonist with a Ki of 3.9, 2.2, 0.5 and 5.1 nM for D2S, D2L, D3, D4 receptor, respectively. IC50 Value: 3.9 nM(D2S); 2.2 nM(D2L); 0.5 nM(D3); 5.1 nM(D4)Target: Dopamine ReceptorPramipexole dihydrochloride is a dopamine receptor agonist with selectivity for the D3 receptor (Ki values are 3.9, 3.3, 0.5 and 3.9 nM for D2L, D2S, D3 and D4 receptors respectively). Pramipexole dihydrochloride exhibits negligable affinity for D1 and D5 receptors. Pramipexole has been found to have neuroprotective effects independent of its dopamine receptor agonism. It reduces mitochondrial reactive oxygen species (ROS) production and inhibits the activation of apoptotic pathways. Pramipexole displays activity in the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS).
Glycopyrrolate(Glycopyrronium Br) is a muscarinic competitive antagonist used as an antispasmodic.IC50 Value:Target: mAChR (Muscarinic acetylcholine receptor M1)in vitro: Glycopyrrolate showed no selectivity in its binding to the M1-M3 receptors. Kinetics studies, however, showed that glycopyrrolate dissociates slowly from HASM muscarinic receptors (60% protection against [3H]-NMS binding at 30 nM) compared to ipratropium bromide [1].in vivo: Glycopyrrolate (1 mg) tablets were then administered, starting with one tablet daily the third week and increasing the daily dose by one tablet per week until a maximum of four tablets during week six and 4 days of week seven when the daily dose was reduced to two tablets for 3 days. glycopyrrolate can be given in controlled doses provided that an adequate medical assessment has been undertaken [2]. Glycopyrrolate has a slow and erratic absorption from the gastrointestinal system, but even low plasma levels are associated with a distinct and long-lasting antisialogic effect [3]. Oral glycopyrrolate is emerging as a potential second-line treatment option, but experience with safety, efficacy, and dosing is especially limited in children [4]. phase III study, 52.3% of glycopyrrolate oral solution recipients (aged 3-18 years; n = 137) had an mTDS response (primary endpoint); the response rate was consistently above 50% at all 4-weekly timepoints, aside from the first assessment at week 4 (40.3%). In general, glycopyrrolate oral solution was well tolerated in clinical trials. The majority of adverse events were within expectations as characteristic anticholinergic outcomes [5].Toxicity: Side effects include dry mouth, difficult urinating, heachaches, diarrhea and constipation. The medication also induces drowsiness or blurred vision. LD50=709 mg/kg (rat, oral).
L-Phenylalanine-3-13C ((S)-2-Amino-3-phenylpropionic acid-3-13C) is the 13C-labeled L-Phenylalanine. L-Phenylalanine ((S)-2-Amino-3-phenylpropionic acid) is an essential amino acid isolated from Escherichia coli. L-Phenylalanine is a α2δ subunit of voltage-dependent Ca+ channels antagonist with a Ki of 980 nM. L-phenylalanine is a competitive antagonist for the glycine- and glutamate-binding sites of N-methyl-D-aspartate receptors (NMDARs) (KB of 573 μM ) and non-NMDARs, respectively. L-Phenylalanine is widely used in the production of food flavors and pharmaceuticals[1][2][3][4].
Scoulerine ((-)-Scoulerine), an isoquinoline alkaloid, is a potent antimitotic compound. Scoulerine is also an inhibitor of BACE1 (ß-site amyloid precursor protein cleaving enzyme 1). Scoulerine inhibits proliferation, arrests cell cycle, and induces apoptosis in cancer cells[1].
BACE1-IN-6 is a BACE1 inhibitor with an IC50 value of 1.5 nM.
NPEC- caged-(S)-AMPA, a caged neurotransmitter analog, is a NPEC photoprotecting group caged the (S)-AMPA (HY-100815A) to make caged ligands specific for glutamate receptor sub-types. NPEC- caged-(S)-AMPA selectively activates AMPA receptor[1].
AM 374 is an fatty acid amide hydrolase (FAAH) inhibitor. AM 374 inhibits amidase activity with an IC50 value of 13 nM. AM 374 can be used for the research of neurological disease[1][2].
Malathion is an organophosphate parasympathomimetic which binds irreversibly to cholinesterase, is an insecticide of relatively low human toxicity.
STO-609 is a selective and cell-permeable inhibitor of the Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK), with Ki values of 80 and 15 ng/mL for recombinant CaM-KKα and CaM-KKβ, respectively.
RPR104632 is a specific antagonist of NMDA receptor, with potent neuroprotective properties.
Tegileridine is the potent agonist of opioid receptor (MOR). Tegileridine is an oxa spiro derivative which reduces the side effects mediated by β-arrestin. Tegileridine has the potential for the research of pains and pains-related diseases (extracted from patent WO2017063509A1)[1].
Fosthiazate is a broad-spectrum nematicide against various plant parasitic nematodes, including Meloidogyne spp., Globodera spp., and Pratylenchus spp., through inhibiting the synthesis of acetylcholinesterase[1].
Haloperidol D4' is deuterium labeled haloperidol, and the latter is a potent dopamine D2 receptor antagonist.
24-Hydroxycholesterol is a natural sterol, which serves as a positive allosteric modulator of N-Methyl-d-Aspartate (NMDA) receptorsR, and a potent activator of the transcription factors LXR.
Nociceptin (1-13), amide is a potent ORL1 (OP4) receptor agonist with a pEC50 of 7.9 for mouse vas deferens and a Ki of 0.75 nM for binding to rat forebrain membranes[1][2].
[D-Ala2]-Met-Enkephalin, an opioid peptide, is a potent opioid agonist. [D-Ala2]-Met-Enkephalin inhibits ACh-induced and suckling-induced oxytocin (OT) release[1][2].
Loxapine Succinate is a D2DR and D4DR inhibitor, serotonergic receptor antagonist and also a dibenzoxazepine anti-psychotic agent.IC50 value: Target: D2DR/D4DR; 5-HT receptorin vitro: In the presence of Loxapine, [3H]ketanserin binds to 5-HT2 receptor in Frontal cortex of brain in human and bovine with ki value of 6.2 nM and 6.6 nM, respectively. Loxapine has the rank order of potency for the various receptors appears to be as follows:5-HT2≥D4>>>D1>D2 in comparing competition experiments involving the human membranes [1]. Loxapine 0.2 μM, 2 μM and 20 μM reduces IL-1beta secretion by LPS-activated mixed glia cultures after 1 and 3 days of exposure. Loxapine in concentrations of 0.2 μM, 2 μM and 20 μM reduces IL-2 secretion in mixed glia cultures after 1 and 3 days of exposure, and additionally Loxapine decreases IL-1beta and IL-2 secretion in LPS-induced microglia cultures in concentrations of 2 μM, 10 μM and 20 μM [2].in vivo: Loxapine (5 mg/kg) induces a very significant reduction (more than 50%) of serotonin (S2) receptor density after 4 weeks or 10 weeks of daily injection in the rat. Loxapine (5 mg/kg) does not change dopamine receptor density but greatly reduces serotonin receptor density by 47% in the brain of rats [3].
Lazabemide hydrochloride (Ro 19-6327 hydrochloride) is a selective, reversible inhibitor of monoamine oxidase B (MAO-B) (IC50=0.03 μM) but less active for MAO-A (IC50>100 μM). Lazabemide inhibits monoamine uptake at high concentrations, the IC50 values are 86 μM, 123 μM and >500 μM for noradrenalin, serotonin and dopamine uptake, respectively. Lazabemide can be used for the research of parkinson and alzheimer′s disease[1].
(+)-Bicuculline is a light-sensitive competitive antagonist of GABA-A receptor.
ABT-670 is a selective, oral bioavailable agonist of dopamine D4 receptor, with EC50 of 89 nM, 160 nM, and 93 nM for human D4, ferret D4, and rat D4, respectively.
L-Glutamic acid-5-13C is the 13C-labeled L-Glutamic acid. L-Glutamic acid acts as an excitatory transmitter and an agonist at all subtypes of glutamate receptors (metabotropic, kainate, NMDA, and AMPA). L-Glutamic acid shows a direct activating effect on the release of DA from dopaminergic terminals.
NS-102 is a selective kainate (GluK2) receptors antagonist. NS-102 is a potent GluR6/7 receptor antagonist[1][2][3].
Transcrocetin (trans-Crocetin), extracted from saffron (Crocus sativus L.), acts as an NMDA receptor antagonist with high affinity.
SCH-23390-d3 (R-(+)-SCH-23390-d3) hydrochloride is the deuterium labeled SCH-23390 hydrochloride. SCH-23390 hydrochloride (R-(+)-SCH-23390 hydrochloride) is a potent and selective dopamine D1-like receptor antagonist with Kis of 0.2 nM and 0.3 nM for the D1 and D5 receptor, respectively. SCH-23390 hydrochloride is a potent and high efficacy human 5-HT2C receptor agonist with a Ki of 9.3 nM. SCH-23390 hydrochloride also binds with high affinity to the 5-HT2 and 5-HT1C receptors. SCH-23390 hydrochloride inhibits G protein-coupled inwardly rectifying potassium (GIRK) channels with an IC50 of 268 nM[1][2][3].
BU226 hydrochloride is a selective imidazoline 2 (I2) receptors ligand with an Ki of 1.4 nM for I2 and an IC50 of 534.5 nM for I1. BU226 hydrochloride can be used for researching antidepressant[1].
Arecoline Hydrobromide is a muscarinic acetylcholine receptor agonist. Target: mAChRArecoline is an alkaloid found in the areca nut. Arecoline. a drug obtained from the Areca Catechu L., induced a dose-dependent antinociception (0.3-1 mg kg(-1) i.p.) which was prevented by the muscarinic antagonists pirenzepine (0.1 microg per mouse i.c.v.) and S-(-)-ET-126 (0.01 microg per mouse i.c.v.) [1]. Arecoline exerts its excitatory actions by binding to M2-muscarinic receptors on the cell membrane of neurons of the locus coeruleus [2]. Arecoline (1 nM - 1 microM) produced a concentration-dependent contraction in both the longitudinal and the circular smooth muscle of rabbit colon. Atropine (10 microM) abolished the arecoline (80 nM)--induced contraction. M3 receptor antagonist, 4 - DAMP (0.4 microM), abolished the arecoline (80 nM)--related response, whereas M2 receptor antagonist, gallamine (0.4 microM), did not affect the effect of arecoline. These results suggest that arecoline excites the colonic motility via M3 receptor in rabbits [3].
CGP36216 (Compound 9) is a GABAB receptor antagonist. CGP36216 binds to GABAB receptor with a Ki value of 0.3 μM. CGP36216 can be used for research of anxiety and trauma-related disorders[1][2].