Neuronal Signaling is involved in the regulation of the mechanics of the central nervous system such as its structure, function, genetics and physiology as well as how this can be applied to understand diseases of the nervous system. Every information processing system in the CNS is composed of neurons and glia, neurons have evolved unique capabilities for intracellular signaling (communication within the cell) and intercellular signaling (communication between cells).

G protein-coupled receptors (GPCRs), including 5-HT receptor, histamine receptor, opioid receptor, and etc, are the largest class of sensory proteins and are important therapeutic targets in Neuronal Signaling. GPCRs are activated by diverse stimuli, including light, enzymatic processing of their N-termini, and binding of proteins, peptides, or small molecules such as neurotransmitters, and regulate neuronal excitability by indirectly modulating the function of voltage-gated channels, such as voltage-gated calcium channel and transient receptor potential (TRP) ion channels. Besides, Notch signaling, such as β- and γ-secretase, also plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation.

GPCR dysfunction caused by receptor mutations and environmental challenges contributes to many neurological diseases. Notch signaling in neurons, glia, and NSCs is also involved in pathological changes that occur in disorders such as stroke, Alzheimer's disease and CNS tumors. Thus, targeting Neuronal Signaling, such as notch signaling and GPCRs, can be used as therapeutic interventions for several different CNS disorders.

References:
[1] Lathia JD, et al. J Neurochem. 2008 Dec;107(6):1471-81.
[2] Palczewski K, et al. Annu Rev Neurosci. 2013 Jul 8;36:139-64.
[3] Geppetti P, et al. Neuron. 2015 Nov 18;88(4):635-49.


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GR 159897

GR 159897 is a highly potent, selective, competitive, brain-penetrated non-peptide antagonist at tachykinin NK2 receptors, inhibits binding of [3H]GR100679 to hNK2-CHO cells and rat colon membranes with pKis of 9.51 and 10, respectively. Antagonizes bronchoconstriction, with anxiolytic-like activity[1].

  • CAS Number: 158848-32-9
  • MF: C23H27FN2O2S
  • MW: 414.54
  • Catalog: Neurokinin Receptor
  • Density: 1.29g/cm3
  • Boiling Point: 600.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 316.8ºC

Syk inhibitor II

Syk Inhibitor II is a potent, high selective and ATP-competitive Syk inhibitor with an IC50 of 41 nM. Syk Inhibitor II inhibits 5-HT release from RBL-cells with an IC50 of 460 nM. Syk Inhibitor II shows less potent against other kinases and has anti-allergic effect[1].

  • CAS Number: 726695-51-8
  • MF: C14H15F3N6O
  • MW: 340.304
  • Catalog: 5-HT Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 541.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 281.4±32.9 °C

Viminol

Viminol is a centrally acting analgesic agent. Viminol also shows antitussive activity[1][2].

  • CAS Number: 21363-18-8
  • MF: C21H31ClN2O
  • MW: 362.94
  • Catalog: Opioid Receptor
  • Density: 1.07g/cm3
  • Boiling Point: 321.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 148.1ºC

Domperidone

Domperidone is a dopamine blocker and an antidopaminergic reagent.Target: Dopamine ReceptorDomperidone is a useful alternative to metoclopramide for treatment of gastroparesis due to better tolerability. Effectiveness and side-effects from domperidone may be influenced by patient-related factors including polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and domperidone targets [1]. Domperidone is a dopamine D(2) receptor antagonist, which has been used as antiemetic agent in human beings. The percentage recovery of domperidone from wastewater was 95.0%. Celiprolol was used as the internal standard to access the percentage extraction of domperidone from wastewater [2]. Domperidone, a dopamine antagonist that does not easily cross the blood-brain barrier, is considered the gold standard for treating gastrointestinal symptoms in patients with Parkinson's disease (PD) because the risk of developing extrapyramidal adverse effects is considered minimal [3].

  • CAS Number: 57808-66-9
  • MF: C22H24ClN5O2
  • MW: 425.911
  • Catalog: Dopamine Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 723.6±70.0 °C at 760 mmHg
  • Melting Point: 242.5ºC
  • Flash Point: 391.4±35.7 °C

(Rac)-VU 6008667

Rac-VU 6008667 is a selective negative allosteric modulator of muscarinic acetylcholine receptor subtype 5 (M5 NAM) with IC50s of 1.2 μM and 1.6 μM for human M5 and rat M5, respectively. Rac-VU 6008667 has high CNS penetration[1].

  • CAS Number: 2092917-63-8
  • MF: C24H17ClF2N2O2
  • MW: 438.85
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosnetupitant chloride monohydrochloride

Fosnetupitant chloride monohydrochloride (Pronetupitant chloride monohydrochloride) is an NK1 antagonist with pKi values of 9.5, 6.1 for human NK1 and NK3 receptor, respectively. Fosnetupitant chloride monohydrochloride is a methylene phosphate prodrug of Netupitant[1].

  • CAS Number: 1643757-72-5
  • MF: C31H37Cl2F6N4O5P
  • MW: 761.52
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ditryptophenaline

Ditryptophenaline ((-)-Ditryptophenaline) is the metabolites of Aspergillus flavus. Ditryptophenaline inhibits substance P receptor and has anti-inflammatory activity[1].

  • CAS Number: 64947-43-9
  • MF: C42H40N6O4
  • MW: 692.80500
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cevimeline hydrochloride hemihydrate

Cevimeline hydrochloride hemihydrate, a novel muscarinic receptor agonist, is a candidate therapeutic drug for xerostomia in Sjogren's syndrome. IC50 value:Target: mAChRThe general pharmacol. properties of this drug on the gastrointestinal, urinary, and reproductive systems and other tissues were investigated in mice, rats, guinea pigs, rabbits, and dogs. The in vitro metab. of SNI-2011 was also evaluated with rat and dog liver microsomes. After oral administration, plasma concns. of SNI-2011 reached to Cmax within 1 h in both species, suggesting that SNI-2011 was quickly absorbed, and then decreased with a t1/2 of 0.4-1.1 h. The bioavailability was 50% and 30% in rats and dogs, resp. Major metabolites in plasma were both S- and N-oxidized metabolites in rats and only N-oxidized metabolite in dogs, indicating that a large species difference was obsd. in the metab. of SNI-2011. Sex difference was also obsd. in the pharmacokinetics of SNI-2011 in rats, but not in dogs. In the in vitro study, chem. inhibition and pH-dependent studies revealed that the sulfoxidn. and N-oxidn. of SNI-2011 were mediated by cytochrome P 450 (CYP) and flavin-contg. monooxygenase (FMO), resp., in both species. In addn., CYP2D and CYP3A were mainly responsible for the sulfoxidn. in rat liver microsomes.

  • CAS Number: 153504-70-2
  • MF: C20H35ClN2O2S2
  • MW: 435.09
  • Catalog: mAChR
  • Density: 1.19g/cm3
  • Boiling Point: 308.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 140.4ºC

SB 399885 hydrochloride

SB-399885 hydrochloride is a 5-HT6 receptor antagonist.

  • CAS Number: 402713-81-9
  • MF: C18H22Cl3N3O4S
  • MW: 482.809
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gavestinel

Gavestinel (GV 150526) is a selective and potent the glycine site of the NMDA receptor antagonist. Gavestinel has neuroprotectant effects[1].

  • CAS Number: 153436-22-7
  • MF: C18H12Cl2N2O3
  • MW: 375.21
  • Catalog: iGluR
  • Density: 1.561g/cm3
  • Boiling Point: 701.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 377.8ºC

Azemiopsin

Azemiopsin is a potent nicotinic acetylcholine receptor (nAChR) inhibitor with IC50s of 0.18 μM and 22 μM against T. californica nAChR and human α7 nAChR, respectively. Azemiopsin blocks acetylcholine-induced currents in Xenopus oocytes heterologously expressing human muscle-type nAChR[1].

  • CAS Number: 1391936-86-9
  • MF: C118H174N38O26
  • MW: 2540.88
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-chloro-1-[1-[3-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)propyl]piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one maleate

Domperidone (R33812) monomaleate is an orally active and selective dopamine-2 receptor antagonist. Domperidone monomaleate acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine[1].

  • CAS Number: 83898-65-1
  • MF: C26H28ClN5O6
  • MW: 541.98300
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

metoclopramide hydrochloride

Metoclopramide hydrochloride hydrate is a dopamine D2 antagonist that is used as an antiemetic.IC50 Value:Target: D2 ReceptorMetoclopramide is a dopamine receptor antagonist which has been used for treatment of a variety of gastrointestinal symptoms over the last thirty years. In various countries, metoclopramide is the antiemetic drug of choice in pregnant women. Findings provide reassurance regarding the safety of metoclopramide for the fetus when the drug is given to women to relieve nausea and vomiting during pregnancy. Evidence also supports its use for gastroparesis (poor stomach emptying) and gastroesophageal reflux disease. It appears to bind to dopamine D2 receptors where it is a receptor antagonist, and is also a mixed 5-HT3 receptor antagonist/ 5-HT4 receptor agonist.

  • CAS Number: 54143-57-6
  • MF: C14H25Cl2N3O3
  • MW: 354.27
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 418.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 207ºC

Leu-Enkephalin

[Leu5]-Enkephalin is a pentapeptides with morphine like properties. [Leu5]-Enkephalin is a five amino acid endogenous peptide that acts as an agonist at opioid receptors.

  • CAS Number: 58822-25-6
  • MF: C28H37N5O7
  • MW: 555.62300
  • Catalog: Peptides
  • Density: 1.274 g/cm3
  • Boiling Point: 998.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 557.8ºC

CGP 64213

CGP 64213 is a GABAb receptor agonist.

  • CAS Number: 200402-50-2
  • MF: C26H36IN2O7P
  • MW: 646.45
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-689,560

L-689560 is a potent N-methyl-D-aspartate (NMDA) receptor antagonist at the GluN1 glycine binding site. L-689560 is widely used as a radiolabeled ligand in binding studies and used for study the roles of NMDA receptors in normal neurological processes as well as in diseases[1][2].

  • CAS Number: 139051-78-8
  • MF: C17H15Cl2N3O3
  • MW: 380.22500
  • Catalog: iGluR
  • Density: 1.51g/cm3
  • Boiling Point: 549.1ºC at 760 mmHg
  • Melting Point: 172-173ºC
  • Flash Point: 285.9ºC

Flavoxate-d4 hydrochloride

Flavoxate-d4 hydrochloride (Rec-7-0040-d4) is the deuterium labeled Flavoxate hydrochloride. Flavoxate Hydrochloride is a muscarinic AChR antagonist used in various urinary syndromes and as an antispasmodic[1][2].

  • CAS Number: 1189678-43-0
  • MF: C24H22ClD4NO4
  • MW: 431.94500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Roxindole

Roxindole (EMD 49980), an indot-alkyl-pipenidine, is a potent agonist at dopamine autoreceptors, with an affinity for the D2-like subtype in the low nanomolar range. Roxindole can be used for the research of positive and negative schizophrenic symptoms. Roxindole is a 5-HT1A agonist and 5-HT uptake inhibitor with high affinity for 5-HT1A (IC50=0.9 nM). Antipsychotic and antidepressant activities[1][2][3].

  • CAS Number: 112192-04-8
  • MF: C23H26N2O
  • MW: 346.47
  • Catalog: Dopamine Receptor
  • Density: 1.173g/cm3
  • Boiling Point: 575.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 302ºC

Picfeltarraenin X

Picfeltarraenin X, a triterpenoid isolated from Picria fel-terrae Lour, is an AChE inhibitor[1].

  • CAS Number: 1391826-61-1
  • MF: C36H54O11
  • MW: 662.807
  • Catalog: AChE
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 800.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 245.4±27.8 °C

Raclopride-d5 hydrochloride

Raclopride-d5 (hydrochloride) is the deuterium labeled Raclopride. Raclopride is a dopamine D2/D3 receptor antagonist, which binds to D2 and D3 receptors with dissociation constants (Kis) of 1.8 nM and 3.5 nM, respectively, but has a very low affinity for D1 and D4 receptors with Kis of 18000 nM and 2400 nM, respectively[1][2].

  • CAS Number: 1217623-85-2
  • MF: C15H16D5Cl3N2O3
  • MW: 352.27
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ebeiedinone

Ebeiedinone, a steroidal alkaloid from Fritillaria species, inhibits the bioactivity of human whole blood cholinesterase (ChE) at the concentration of 0.1 mM, with the inhibitory effects of 69.0%[1].

  • CAS Number: 25650-68-4
  • MF: C27H43NO2
  • MW: 413.63600
  • Catalog: AChE
  • Density: 1.13±0.1 g/cm3
  • Boiling Point: 536.4±35.0 °C
  • Melting Point: N/A
  • Flash Point: N/A

Eletriptan-d3

Eletriptan-d3 (Eletriptan-d3 HBr) is the deuterium labeled Eletriptan hydrobromide. Eletriptan hydrobromide is a selective 5-HT1B and 5-HT1D receptor agonist with Ki of 0.92 nM and 3.14 nM, respectively[1][2].

  • CAS Number: 1287040-94-1
  • MF: C22H23D3N2O2S
  • MW: 385.54
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-00217830

PF-00217830 is a serotonin 1A receptor agonist, dopamine D2 receptor agonist, and serotonin 2A receptor antagonist.PF-00217830 may be used in the study of schizophrenia.

  • CAS Number: 846032-02-8
  • MF: C26H30N4O2
  • MW: 430.54
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Artanin

Artanin is a coumarin, has biological activities related to Alzheimer’s disease. Artanin exerts function including AChE inhibitory and AChE- and self-induced amyloid beta (Aβ) aggregation inhibitory activities, with IC50s of 51 μM, 98 μM, and 124 μM, respectively[1].

  • CAS Number: 96917-26-9
  • MF: C16H18O5
  • MW: 290.311
  • Catalog: AChE
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 460.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 204.9±28.8 °C

Piboserod

Piboserod (SB 207266) is a selective 5-HT(4) receptor antagonist.IC50 value:Target: 5-HT4 antagonistin vitro: Piboserod did not modify the basal contractions but concentration-dependently antagonized the ability of 5-HT to enhance bladder strip contractions to EFS. In presence of 1 and 100 nM of piboserod, the maximal 5-HT-induced potentiations were reduced to 45.0+/-7.9 and 38.7+/-8.7%, respectively [1].in vivo: Piboserod significantly increased LVEF by 1.7% vs. placebo (CI 0.3, 3.2, P = 0.020), primarily through reduced end-systolic volume from 165 to 158 mL (P = 0.060). There was a trend for greater increase in LVEF (2.7%, CI -1.1, 6.6, P = 0.15) in a small subset of patients not on chronic beta-blocker therapy. There was no significant effect on neurohormones, quality of life, or exercise tolerance. Patients on piboserod reported more adverse events, but numbers were too small to identify specific safety issues [2]. Pretreatment with potent 5-HT4 ligands dose-dependently reduced striatal SB207145 concentration and the effective dose to achieve 50% receptor occupancy (ED50 ) values were 4.8, 2.0, 7.4, 9.9, 3.8 and 0.02?mg/kg for GR113808, piboserod, prucalopride, RS67333, TD8954 and PF04995274, respectively [3].

  • CAS Number: 152811-62-6
  • MF: C22H31N3O2
  • MW: 369.50000
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AChE-IN-3

AChE-IN-3 shows moderate inhibitory activity against AChE and strong NO inhibitory activity with an EC50 of 0.57 μM.

  • CAS Number: 2713548-95-7
  • MF: C25H21N3O4
  • MW: 427.45
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[D-Arg1,D-Pro2,D-Phe7,D-His9]-Substance P

(D-Arg1,D-Pro2,D-Phe7,D-His9)-Substance P is a selective NK1 receptor antagonist[1].

  • CAS Number: 115760-58-2
  • MF: C67H102N20O13S
  • MW: 1427.72000
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BACE1-IN-12

BACE1-IN-12 (compound 7g) is a potent and BBB-penetrated BACE1 inhibitor, with an IC50 of 8.9 µM. BACE1-IN-12 shows selective BuChE (butyrylcholinesterase) inhibitory activity with an IC50 of 3.2 µM. BACE1-IN-12 shows effective antioxidant effect with an IC50 of 10.2 μM (DPPH). BACE1-IN-12 might be served as a potential anti-Alzheimer agent[1].

  • CAS Number: 2479315-19-8
  • MF: C29H28Cl2N6O
  • MW: 547.48
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MAO-B-IN-11

MAO-B-IN-11 (Compound 8c) is a potent monoamine oxidase B (MAO-B) inhibitor with an IC50 of 1.3 μM. MAO-B-IN-11 shows a neuroprotective activity[1].

  • CAS Number: 192383-78-1
  • MF: C22H32O3
  • MW: 344.49
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB-399885

SB399885 is a potent, selective, brain penetrant and orally active 5-HT6 receptor antagonist with pKi values 9.11 and 9.02 for human recombinant and native 5-HT6 receptors, respectively. SB399885 has cognitive enhancing properties[1].

  • CAS Number: 402713-80-8
  • MF: C18H21Cl2N3O4S
  • MW: 446.34800
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A