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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ondansetron-d3

Ondansetron-d3 is the deuterium labeled Ondansetron[1]. Ondansetron(GR 38032;SN 307) is a serotonin 5-HT3 receptor antagonist used mainly as anantiemetic (to treat nausea and vomiting), often following chemotherapy[2].

  • CAS Number: 1132757-82-4
  • MF: C18H16D3N3O
  • MW: 296.38100
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Endovalpin

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].

  • CAS Number: 80-50-2
  • MF: C27H43NO9
  • MW: 525.63200
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 329ºC
  • Flash Point: N/A

Monepantel

Monepantel is organic anthelmintic, and acts as a positive allosteric modulator of a nematode-specific clade of nicotinic acetylcholine receptor (nAChR) subunits.

  • CAS Number: 887148-69-8
  • MF: C20H13F6N3O2S
  • MW: 473.39200
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Decanoic acid-d5

Decanoic acid-d5 is the deuterium labeled Decanoic acid. Decanoic acid, a component of medium chain triclycerides, is a brain-penetrant and non-competitive inhibitor of AMPA receptor. Decanoic acid has antiseizure effects[1][2][3].

  • CAS Number: 1219803-00-5
  • MF: C10H15D5O2
  • MW: 177.30
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aβ-IN-5

Aβ-IN-5 (Compound e12) is an orally active Aβ aggregation inhibitor. Aβ-IN-5 also inhibits AChE and BuChE with IC50 values of 21.29 μM and 1.32 μM, respectively. Aβ-IN-5 shows excellent neuroprotective effects and low neurotoxicity[1].

  • CAS Number: 2417977-65-0
  • MF: C21H20N2O3
  • MW: 348.40
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aripiprazole monohydrate

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].

  • CAS Number: 851220-85-4
  • MF: C23H29Cl2N3O3
  • MW: 466.40100
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB 271046 (Hydrochloride)

SB271046 Hcl is a potent, selective and orally active 5-HT6 receptor antagonist with pKi of 8.9.IC50 Value: 8.9(pKi)Target: 5-HT6 Receptorin vitro: SB 271046 hydrochloride is a sulfonamidal benzothiophene derivative that has been shown to act as a selective 5-HT6 antagonist with pKi values of 9.02-8.92, 6.55, 6.35, 6.27, 6.05, 5.95, 5.76, 5.73, 5.62, 5.55, 5.41, 5.39, 5.27 and < 4.99 for 5-HT6, 5-HT1D, 5-HT1A, D3, 5-HT1B, 5-HT1F, α1B, 5-HT2C, 5-HT2A, D2, 5-HT2B, 5-HT7, 5-HT4 and 5-HT1E respectively, and is > 200-fold selective over 55 other receptors, enzymes and ion channels.in vivo: SB-271046 is moderately brain penetrant (10%), subject to low blood clearance (7.7 mL/min/kg) with a good half-life in rats (4.8 hours), and has excellent oral bioavailability (>80%). SB-271046 produces 3-fold and 2-fold increases in extracellular glutamate levels in both frontal cortex and dorsal hippocampus of rats, respectively, which may be used for the treatment of cognitive and memory dysfunction. SB-271046 (20 mg/kg, orally gavage) 30 min prior to training Wistar rats, is found to reverse significantly the amnesia produced by administering scopolamine (0.8 mg/kg, i.p.) in the 6 hours post-training period. SB-271046 progressively and significantly decreases platform swim angle and escape latencies over the five sequential trials on four consecutive daily sessions compared to vehicle-treated controls in aged rats. SB-271046 also improves task recall as measured by significant increases in the searching of the target quadrant on post-training days 1 and 3. SB-271046 (10 mg/kg, s.c.) produces a significant, tetrodotoxin-dependent, increase in extracellular levels of both glutamate and aspartate within the frontal cortex of rats, reaching maximum values of 375.4% and 215.3% of preinjection values, respectively.

  • CAS Number: 209481-24-3
  • MF: C20H23Cl2N3O3S2
  • MW: 488.45
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TIPP

TIPP is a potent and selective δ-opioid antagonist with a Ki value of 1.22 nM[1].

  • CAS Number: 146369-65-5
  • MF: C37H38N4O6
  • MW: 634.72
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cyclobuxine D

Cyclobuxine D is a steroidal alkaloid extracted from Buxus microphylla. Cyclobuxine D has a significant bradycardic effect in the rat heart and an inhibitory action on acetylcholine and Ba++−induced contraction of the longitudinal muscle isolated from the rabbit jejunum[1][2].

  • CAS Number: 2241-90-9
  • MF: C25H42N2O
  • MW: 386.61400
  • Catalog: mAChR
  • Density: 1.08g/cm3
  • Boiling Point: 494.2ºC at 760mmHg
  • Melting Point: 236-238ºC
  • Flash Point: 53.5ºC

LY3202626

LY3202626 is a small molecule non-selective BACE1 inhibitor, causes dose-dependent reductions in CSF and plasma Aβ concentrations, shows potential for the treatment of Alzheimer's disease. Alzheimer Disease Phase 2 Clinical

  • CAS Number: 1628690-73-2
  • MF: C22H20F2N8O2S
  • MW: 498.508
  • Catalog: Beta-secretase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNE-9278

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].

  • CAS Number: 2315311-83-0
  • MF: C21H27N5O3S
  • MW: 429.54
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UBP710

UBP710 is a selective NMDA receptor modulator. UBP710 displays greater activity in potentiating GluN2B-containing receptors than those containing GluN2A[1].

  • CAS Number: 1333111-40-2
  • MF: C18H14O2
  • MW: 262.303
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 488.3±14.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 217.6±14.8 °C

2-Chloro-3-(trifluoromethyl)-N-((S)-phenyl((S)-piperidin-2-yl)methyl)benzamide hydrochloride

SSR504734 is an orally active, selective and reversible inhibitor of human, rat, and mouse GlyT1 (IC50=18, 15, and 38 nM, respectively). SSR504734 shows anti-schizophrenia, anti-anxiety and anti-depression activities[1].

  • CAS Number: 615571-23-8
  • MF: C20H21Cl2F3N2O
  • MW: 433.29500
  • Catalog: GlyT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vigabatrin

Vigabatrin(γ-Vinyl-GABA; Sabril) is a structural analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) that irreversibly inhibits the catabolism of GABA by GABA transaminase.IC50 value:Target: GABA transaminaseClinical studies have shown that vigabatrin is superior to placebo in decreasing the frequency of infantile spasms. In tuberous sclerosis, vigabatrin may be considered the first-line treatment for IS. The mode of action is increasing concentrations of the inhibitory neurotransmitter GABA in the brain.A significant increase in seizure threshold was observed following systemic (i.p.) administration of high (600 or 1200 mg/kg) doses of vigabatrin. Bilateral microinjection of vigabatrin (10 μg) into either the anterior or posterior SNr also increased seizure threshold, but less markedly than systemic treatment.

  • CAS Number: 68506-86-5
  • MF: C6H11NO2
  • MW: 129.157
  • Catalog: GABA Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 277.7±28.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 121.7±24.0 °C

Pizotifen malate

Pizotifen malate is a potent 5-HT2 receptor antagonist, with a high affinity for 5-HT1C binding site.

  • CAS Number: 5189-11-7
  • MF: C23H27NO5S
  • MW: 429.53
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 436.7ºC at 760 mmHg
  • Melting Point: 185-186° (dec)
  • Flash Point: 217.9ºC

CGP 55845 hydrochloride

CGP55845 hydrochloride is a potent and selective GABAB receptor antagonist with an IC50 of 6 nM. CGP55845 hydrochloride can be used for neurological research[1][2].

  • CAS Number: 149184-22-5
  • MF: C18H22Cl2NO3P
  • MW: 402.25200
  • Catalog: GABA Receptor
  • Density: 1.332g/cm3
  • Boiling Point: 647.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 345.6ºC

β2AR/M3-receptor agonist-1

β2AR/M3-receptor agonist-1 (example 9) is a potent β2AR and M3 receptor agonist. β2AR/M3-receptor agonist-1 shows M3 receptor affinity with a pIC50 value of 9.3. β2AR/M3-receptor agonist-1 has the potential for the research of respiratory tract disorders[1].

  • CAS Number: 1206887-00-4
  • MF: C38H40N4O7.xCH2O2
  • MW:
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Imipramine-d6

Imipramine-d6 is the deuterium labeled Imipramine hydrochloride. Imipramine hydrochloride inhibits serotonin transporter with an IC50 value of 32 nM. Imipramine hydrochloride is reported to prevent the translocation of aSMase, inhibiting MV and exosomes secretion[1][2][3][4][5].

  • CAS Number: 65100-45-0
  • MF: C19H18D6N2
  • MW: 286.44400
  • Catalog: Serotonin Transporter
  • Density: 1.064g/cm3
  • Boiling Point: 403.089ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 179.73ºC

Tedatioxetine (hydrobromide)

Tedatioxetine hydrobromide acts as a triple reuptake inhibitor and 5-HT2A, 5-HT2C, 5-HT3 and α1A-adrenergic receptor antagonist.

  • CAS Number: 960151-65-9
  • MF: C18H22BrNS
  • MW: 364.34300
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Modaline sulfate

Modaline Sulfate is a MAO inhibitor, used in the treatment of depression.

  • CAS Number: 2856-75-9
  • MF: C10H17N3O4S
  • MW: 275.32500
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: 294.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 131.7ºC

NEO 376

NEO 376 is a selective modulator of 5-HT1 receptor, GABA receptor and dopamine receptor, with anti-psychotic actively.

  • CAS Number: 496921-73-4
  • MF: C20H24ClN3O
  • MW: 357.877
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 547.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 285.1±30.1 °C

Heliosupine

Heliosupine is a pyrrolizidine alkaloid. Heliosupine is an acetylcholinesterase (AChE) inhibitor, with an IC50 0.57 mM. Heliosupine exhibits deterrent effects against generalist herbivores[1][2].

  • CAS Number: 32728-78-2
  • MF: C20H31NO7
  • MW: 397.46300
  • Catalog: AChE
  • Density: 1.26g/cm3
  • Boiling Point: 535.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 277.8ºC

Ambutonium bromide

Ambutonium bromide is an acetylcholine antagonist.

  • CAS Number: 115-51-5
  • MF: C20H27BrN2O
  • MW: 391.34500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Clorpyrifos

Chlorpyrifos is an organophosphate insecticide that is classified as a phosphorothionate. The oxon metabolite of Chlorpyrifos is an inhibitor of acetylcholinesterase (AChE), affecting neurological function in insects, humans, and other animals. The Chlorpyrifos oxon (CPO) metabolite is hydrolyzed by the plasma enzyme paraoxonase 1 (PON1), and susceptibility to neurotoxicity associated with CPO exposure is mitigated by PON1 overexpression.

  • CAS Number: 2921-88-2
  • MF: C9H11Cl3NO3PS
  • MW: 350.586
  • Catalog: AChE
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 375.9±52.0 °C at 760 mmHg
  • Melting Point: 42-44°C
  • Flash Point: 181.1±30.7 °C

Arecaidine but-2-ynyl ester tosylate

Arecaidine but-2-ynyl ester tosylate is a potent muscarinic agonist that shows 4.6-fold that is selectivity for mAChR M2 in the atrium versus those in the ileum.

  • CAS Number: 119630-77-2
  • MF: C11H15NO2.C7H8SO3
  • MW: 365.444
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyr-α-CGRP (23-37) (mouse, rat)

[Tyr22] Calcitonin Gene Related Peptide, (22-37), rat is a fragments 22-37 of rat calcitonin gene related peptide (CGRP), targeting CGRP receptor and adenylate cyclase. Calcitonin is mainly produced by thyroid C cells while CGRP is secreted and stored in the nervous system[1].

  • CAS Number: 198277-54-2
  • MF: C82H120N20O25
  • MW: 1785.95000
  • Catalog: Adenylate Cyclase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-Amisulpride

(S)-Amisulpride (Esamisulpride) is a potent dopamine D2/D3 receptor antagonist. (S)-Amisulpride is an antagonist at the 5-HT7 receptor with a KI of 900 nM. (S)-Amisulpride has antipsychotic and antidepressant effects[1][2].

  • CAS Number: 71675-92-8
  • MF: C17H27N3O4S
  • MW: 369.48
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 558.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 291.8±30.1 °C

2-piperidin-1-ylethyl 4-amino-5-chloro-2-methoxybenzoate

ML 10302 is a potent agonist 5-HT4 receptor with Ki of 1.07 nM. 5-Hydroxytryptamine (5-HT4) receptor agonists stimulate gut motility through cholinergic pathways. ML10302 induces significant prokinesia both in the small bowel and colon through activation of cholinergic pathways. ML 10302 also has the potential for the research of neurology diseases[1].

  • CAS Number: 148868-55-7
  • MF: C15H21ClN2O3
  • MW: 312.79200
  • Catalog: 5-HT Receptor
  • Density: 1.223g/cm3
  • Boiling Point: 472.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 239.7ºC

β-Casomorphin, bovine

β-casomorphin, bovine (β-casomorphin-7) is a opioid peptide with an IC50 of 14 μM in an Opioid receptors binding assay.

  • CAS Number: 72122-62-4
  • MF: C41H55N7O9
  • MW: 789.91700
  • Catalog: Peptides
  • Density: 1.32g/cm3
  • Boiling Point: 1170.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 661.7ºC

Afacifenacin

Afacifenacin (SMP-986) is a potent and orally active muscarinic receptor antagonist. Afacifenacin inhibits the bladder afferent pathway through the sodium-channel blockade, increasing volume, and reducing the frequency of urination and incontinence. Afacifenacin has the potential for the research of overactive bladder (OAB)[1][2].

  • CAS Number: 877606-63-8
  • MF: C27H26F3N3O2
  • MW: 481.50900
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A