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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Valnoctamide

Valnoctamide (Valmethamide), a derivative of valproate, suppresses benzodiazepine-refractory status epilepticus. Valnoctamide (Valmethamide) acts directly on GABAA receptors[1].

  • CAS Number: 4171-13-5
  • MF: C8H17NO
  • MW: 143.22700
  • Catalog: GABA Receptor
  • Density: 0.883g/cm3
  • Boiling Point: 274.4ºC at 760mmHg
  • Melting Point: 113.5-114ºC
  • Flash Point: 119.8ºC

5-Hydroxyferulic acid

5-Hydroxyferulic acid is a hydroxycinnamic acid and is a metabolite of the phenylpropanoid pathway. 5-Hydroxyferulic acid is a precursor in the biosynthesis of sinapic acid and is also a COMT non-esterifed substrate[1][2][3].

  • CAS Number: 1782-55-4
  • MF: C10H10O5
  • MW: 210.18300
  • Catalog: COMT
  • Density: 1.44g/cm3
  • Boiling Point: 449.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 182.8ºC
  • CAS Number: 59481-79-7
  • MF: C45H66N10O15S
  • MW: 1019.13000
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Substance P (5-11) trifluoroacetate salt

Substance P (5-11), the C-terminal heptapeptide of Substance P (Substance P (HY-P0201)), is a neuropeptide. Substance P (5-11) binds to NK-1 tachykinin receptor[1].

  • CAS Number: 51165-09-4
  • MF: C41H60N10O9S
  • MW: 869.04200
  • Catalog: Neurokinin Receptor
  • Density: 1.265g/cm3
  • Boiling Point: 1375.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 785.6ºC

5-HT7 agonist 1

5-HT7 agonist 1 is a selective 5-HT7 receptor agonist, with an IC50 of 222.93 nM, can be used for the 5-HT7 receptor related disease, such as CNS disorders.

  • CAS Number: 334974-31-1
  • MF: C19H20ClN3
  • MW: 325.83500
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ocaperidone

Ocaperidone is an effective antipsychotic agent, acting as a potent 5-HT2 and dopamine D2 antagonist, and a 5-HT1A agonist, with Kis of 0.14 nM, 0.46 nM, 0.75 nM, 1.6 nM and 5.4 nM for 5-HT2, a1-adrenergic receptor, dopamine D2, histamine H1 and a2-adrenergic receptor, respectively, and a pEC50 and pKi of 7.60 and 8.08 for h5-HT1A.

  • CAS Number: 129029-23-8
  • MF: C24H25FN4O2
  • MW: 420.47900
  • Catalog: 5-HT Receptor
  • Density: 1.34g/cm3
  • Boiling Point: 588ºC at 760mmHg
  • Melting Point: 180-184°C
  • Flash Point: 309.4ºC

Glycine-13C2

Glycine-13C2 is the 13C-labeled Glycine. Glycine is an inhibitory neurotransmitter in the CNS and also acts as a co-agonist along with glutamate, facilitating an excitatory potential at the glutaminergic N-methyl-D-aspartic acid (NMDA) receptors.

  • CAS Number: 67836-01-5
  • MF: 13C2H5NO2
  • MW: 77.052
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 240ºC (dec.)(lit.)
  • Flash Point: N/A

Flumexadol

Flumexadol is an orally active non-narcotic analgesic. Flumexadol is a selective and affinity 5-HT2C receptor agonist with a Ki of 25 nM for the (+)-enantiomer of Flumexadol, and is 40-fold selective over the 5-HT2A receptor[1][2].

  • CAS Number: 30914-89-7
  • MF: C11H12F3NO
  • MW: 231.21400
  • Catalog: 5-HT Receptor
  • Density: 1.209g/cm3
  • Boiling Point: 271.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 118ºC

RG-12915

RG-12915 is a selective 5-HT3 antagonist, with IC50 value of 0.16 nM.

  • CAS Number: 136174-04-4
  • MF: C20H25ClN2O2
  • MW: 360.878
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 462.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.6±28.7 °C

GABAA receptor agent 1

GABAA receptor agent 1 is a high affinity ligand for GABAA receptor, with potent anticonvulsant activity[1].

  • CAS Number: 1571-87-5
  • MF: C13H8ClN3O2
  • MW: 273.674
  • Catalog: GABA Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 502.1±56.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 257.5±31.8 °C

BACE1-IN-1

BACE1-IN-1 is a potent and highly brain penetrant BACE1 inhibitor with IC50s of 32 and 47 nM for human BACE1 and BACE2, respectively.

  • CAS Number: 1310347-50-2
  • MF: C18H14F3N5O2
  • MW: 389.33
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Org 37684

Org37684 is a highly potent 5-HT2C receptor agonist (pEC50=8.17). Org37684 exhibits a rank order of potency of 5-HT2C>5-HT2B>5-HT2A. Its selectivity for the 5-HT2C receptor is approximately 2.5 times over the 5-HT2B (pEC50=7.96) and ten times for the 5-HT2A (pEC50=7.11) receptor[1].

  • CAS Number: 213007-95-5
  • MF: C14H20ClNO2
  • MW: 269.767
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

β-Secretase Inhibitor I

β-Secretase Inhibitor I is an extremely potent β-secretase inhibitor with reduced cardiovascular and liver toxicity.

  • CAS Number: 1818239-19-8
  • MF: C18H18F3N5O2S
  • MW: 425.43
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GR 128107

GR 128107 is an antagonist of melatonin receptor.

  • CAS Number: 190328-44-0
  • MF: C16H20N2O2
  • MW: 272.34
  • Catalog: Melatonin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cebranopadol ((1α,4α)stereoisomer)

Cebranopadol ((1α,4α)stereoisomer) is a stereoisomer of cebranopadol. Cebranopadol is a potent agonist activity on ORL-1.

  • CAS Number: 863513-93-3
  • MF: C24H27FN2O
  • MW: 378.48
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dasotraline

Dasotraline is a triple reuptake inhibitor that blocks dopamine, norepinephrine, and serotonin transporters with IC50 values of 4, 6, and 11 nM, respectively.

  • CAS Number: 675126-05-3
  • MF: C16H15Cl2N
  • MW: 292.203
  • Catalog: Dopamine Transporter
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 409.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 201.5±28.7 °C

MAO-B-IN-5

MAO-B-IN-5 is a potent, selective and orally active MAO-B inhibitor with an IC50 of 0.204 µM. MAO-B-IN-5 has the potential for the research of Parkinson's disease (PD)[1].

  • CAS Number: 849909-77-9
  • MF: C19H21FN2O2
  • MW: 328.38
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(-)-Borneol

(-)-Borneol has a highly efficacious positive modulating action at GABA receptor with an EC50 of 237 μM.

  • CAS Number: 464-45-9
  • MF: C10H18O
  • MW: 154.249
  • Catalog: GABA Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 212.0±0.0 °C at 760 mmHg
  • Melting Point: 206-209 °C
  • Flash Point: 65.6±0.0 °C

propantheline bromide

Propantheline bromide is an antimuscarinic agent, used for the treatment of hyperhidrosis, cramps or spasms of the stomach, intestines or bladder, and enuresis.

  • CAS Number: 50-34-0
  • MF: C23H30BrNO3
  • MW: 448.393
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 159-161°C
  • Flash Point: N/A

Physostigmine

Physostigmine (Eserine) is a reversible acetylcholinesterase (AChE) inhibitor. Physostigmine can crosses the blood-brain barrier and elevate acetylcholine levels in the brain. Physostigmine can reverse memory deficits in transgenic mice with Alzheimer's disease. Physostigmine is also an antidote for anticholinergic poisoning[1][2][3].

  • CAS Number: 57-47-6
  • MF: C15H21N3O2
  • MW: 275.346
  • Catalog: AChE
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 422.3±55.0 °C at 760 mmHg
  • Melting Point: 102-104 °C(lit.)
  • Flash Point: 209.2±31.5 °C

Zatosetron (maleate)

Zatosetron maleate is a potent and selective 5HT3 receptor antagonist.

  • CAS Number: 123482-23-5
  • MF: C23H29ClN2O6
  • MW: 464.94
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 435.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 216.9ºC

Sombrevin

Propanidid (Sombrevin; Fabantol) is a γ-aminobutyric acid type A (GABAA) receptor agonist and a short-acting non-barbiturate general anesthetic agent. Propanidid can decrease the arterial pressure[1][2].

  • CAS Number: 1421-14-3
  • MF: C18H27NO5
  • MW: 337.41100
  • Catalog: GABA Receptor
  • Density: 1.087g/cm3
  • Boiling Point: 459.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 231.8ºC

QNZ46

QNZ46 is a NR2C/NR2D-selective NMDA receptor non-competitive antagonist (IC50 values are 3, 6, 229, and >300, >300 μM for NR2D, NR2C, NR2A, NR2B, and GluR1, respectively). IC50 value: 3 μM (for NR2D), 6 μM (for NR2C), 229 μM (for NR2D NR2A)Target: NR2D, NR2C, NR2Ain vitro: QNZ46 is a noncompetitive inhibitor of GluN2C/D containing NMDA receptors. KD and IC50 values for binding and inhibition of GluN1/Glun2D receptors by QNZ46 are 4.9 and 3.9 μM, respectively. QNZ46 does not compete for binding of glutamate or glycine, but QNZ46 receptor binding requires the binding of glutamate to the GluN2 subunit.

  • CAS Number: 1237744-13-6
  • MF: C24H17N3O6
  • MW: 443.40800
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

frakefamide

Frakefamide is a potent analgesic that acts as a peripheral active μ-selective receptor agonist. Frakefamide is unable to penetrate the blood-brain-barrier and enter the central nervous system[1][2].

  • CAS Number: 188196-22-7
  • MF: C30H34FN5O5
  • MW: 563.620
  • Catalog: Opioid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 897.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 496.8±34.3 °C

Neoeriocitrin

Neoeriocitrin, isolated from Drynaria Rhizome, shows activity on proliferation and osteogenic differentiation in MC3T3-E1. Neoeriocitrin is a potent acetylcholinesterase (AChE) inhibitor[1][2].

  • CAS Number: 13241-32-2
  • MF: C27H32O15
  • MW: 596.53400
  • Catalog: AChE
  • Density: 1.73g/cm3
  • Boiling Point: 960.7ºC at 760 mmHg
  • Melting Point: 277ºC
  • Flash Point: 318.3ºC

trimipramine

Trimipramine is a 5-HT receptor antagonist, with pKi binding values of 6.39, 8.10, 4.66 for 5-HT1C, 5-HT2 and 5-HT1A, respectively. Trimipramine is also a potent and selective inhibitor targeting human noradrenaline (hNAT), serotonin (hSERT) and organic cation transporters (hOCT1, hOCT2) with IC50 values of 4.99 μM, 2.11 μM, 3.72 μM, 8.00 μM, respectively. Trimipramine has vascular activity and anxiolytic efficacy[1][2][3].

  • CAS Number: 739-71-9
  • MF: C20H26N2
  • MW: 294.43400
  • Catalog: Bacterial
  • Density: 0.9912 (rough estimate)
  • Boiling Point: 426.2°C (rough estimate)
  • Melting Point: 45°
  • Flash Point: 9℃

Elenbecestat

Elenbecestat (E2609) is a novel potent BACE-1 inhibitor for the treatment of Alzheimer's disease (AD)[1].

  • CAS Number: 1388651-30-6
  • MF: C19H18F3N5O2S
  • MW: 437.44
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosaprepitant

Fosaprepitant (L-758298) is a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting.IC50 Value:Target: NK1 receptorin vitro: Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min of intravenous administration via the action of ubiquitous phosphatases. Owing to the rapid conversion offosaprepitant to the active form (aprepitant), fosaprepitant 115 mg provided the same aprepitant exposure in terms of AUC as aprepitant 12 mg orally, and fosaprepitant is expected to provide a correspondingly similar antiemetic effect as aprepitant [1]. in vivo: Fosaprepitant is well tolerated with mild to moderate venous irritation being the only additional toxicity to those seen with oral aprepitant, and that is a function of dose, concentration, and infusion rate [2]. Patients receiving cisplatin ≥ 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1) [3]. Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin [4].

  • CAS Number: 172673-20-0
  • MF: C23H22F7N4O6P
  • MW: 614.407
  • Catalog: Neurokinin Receptor
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 588.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 310ºC

γ-Acetylenic GABA hydrochloride

γ-Acetylenic GABA hydrochloride is a GABA transaminase inhibitor.

  • CAS Number: 103451-26-9
  • MF: C6H10ClNO2
  • MW: 163.6
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

mosapramine

Mosapramine (Clospipramine) is an orally active and potent dopamine receptor antagonist with high affinity to dopamine receptor subtypes 2, 3 and 4, and with moderate affinity for the 5-HT2 receptor. Mosapramine shows antipsychotic activity and can be used in schizophrenia research[1][2].

  • CAS Number: 89419-40-9
  • MF: C28H35ClN4O
  • MW: 479.05700
  • Catalog: Dopamine Receptor
  • Density: 1.29g/cm3
  • Boiling Point: 680.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 365.2ºC