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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Neurokinin B TFA

Neurokinin B TFA belongs to the tachykinin family of peptides. Neurokinin B binds a family of GPCRs-including neurokinin receptor 1 (NK1R), NK2R, and NK3R-to mediate their biological effect[1].

  • CAS Number: 101536-55-4
  • MF: C55H79N13O14S2.2C2HF3O2
  • MW: 1438.47
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Bromocytisine

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].

  • CAS Number: 207390-14-5
  • MF: C11H13BrN2O
  • MW: 269.13800
  • Catalog: nAChR
  • Density: 1.61±0.1 g/cm3(Predicted)
  • Boiling Point: 463.3±45.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

MK-212

MK-212 (CPP) monohydrochloride is a centrally acting 5-HT1C/5-HT2 agonist. MK-212 monohydrochloride can stimulate phosphoinositide hydrolysis in cerebral cortex[1].

  • CAS Number: 61655-58-1
  • MF: C8H12Cl2N4
  • MW: 235.11400
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(1S)-(-)-Alpha-Pinene

(-)-α-Pinene is a monoterpene and shows sleep enhancing property through a direct binding to GABAA-benzodiazepine (BZD) receptors by acting as a partial modulator at the BZD binding site[1].

  • CAS Number: 7785-26-4
  • MF: C10H16
  • MW: 136.234
  • Catalog: GABA Receptor
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 157.9±7.0 °C at 760 mmHg
  • Melting Point: -64ºC
  • Flash Point: 32.2±0.0 °C

CNS-7056

Remimazolam (CNS-7056) is a short-acting GABA(A) receptor agonist[1].

  • CAS Number: 308242-62-8
  • MF: C21H19BrN4O2
  • MW: 439.30500
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tegaserod maleate

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].

  • CAS Number: 189188-57-6
  • MF: C20H27N5O5
  • MW: 417.459
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 661.4ºC at 760 mmHg
  • Melting Point: 180-183ºC
  • Flash Point: 353.8ºC

Loxapine

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].

  • CAS Number: 1977-10-2
  • MF: C18H18ClN3O
  • MW: 327.80800
  • Catalog: 5-HT Receptor
  • Density: 1.2299 (rough estimate)
  • Boiling Point: N/A
  • Melting Point: 109-110°
  • Flash Point: N/A

Mosapride citrate

Mosapride (TAK-370) citrate dehydrate is a gastroprokinetic agent with 5-hydroxytryptamine4 receptor agonist activity and has been widely used in the research of a variety of gastrointestinal disorders. Mosapride citrate dihydrate potently inhibits Kv4.3 in a concentration-dependent manner with IC50 values of 15.2 μM[1]. Mosapride citrate dihydrateselectively stimulates upper GI motility in vivo[2].

  • CAS Number: 636582-62-2
  • MF: C26H33ClFN3O6
  • MW: 538.00800
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 112-114°C
  • Flash Point: N/A

Inaperisone

Inaperisone is a centrally acting muscle relaxant. Inaperisone inhibits the micturition reflex by acting indirectly on GABAB receptors in the brainstem[1].

  • CAS Number: 99323-21-4
  • MF: C16H23NO
  • MW: 245.36000
  • Catalog: GABA Receptor
  • Density: 1.009g/cm3
  • Boiling Point: 370.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 132.5ºC

(D-Pro2,D-Trp6.8,Nle10)-Neurokinin B

(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].

  • CAS Number: 109212-72-8
  • MF: C67H87N15O14
  • MW: 1326.50000
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(±)-Duloxetine hydrochloride

(±)-Duloxetine ((Rac)-Duloxetine) hydrochloride is the racemate of Duloxetine hydrochloride. Duloxetine hydrochloride, a serotonin-norepinephrine reuptake inhibitor, can be used for diabetic neuropathic pain and fibromyalgia as well as major depressive disorder research[1].

  • CAS Number: 947316-47-4
  • MF: C18H20ClNOS
  • MW: 333.87600
  • Catalog: Serotonin Transporter
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FAAH-IN-5

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].

  • CAS Number: 1338575-38-4
  • MF: C21H19N3O6S
  • MW: 441.46
  • Catalog: FAAH
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-1521498

GSK1521498 free base is a potent and selective μ-opioid receptor (MOR) antagonist. GSK1521498 free base is being used for the treatment of disorders of compulsive consumption of food, alcohol, and drugs[1].

  • CAS Number: 1007573-18-3
  • MF: C24H20F2N4
  • MW: 326.34300
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

cyproheptadine hydrochloride

Cyproheptadine is a histamine receptor antagonist for 5-HT2 receptor with IC50 of 0.6 nM. Target: 5-HT2 ReceptorCyproheptadine is a serotonin antagonist and a histamine H2 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. Inhibitory effects of cyclobenzaprine, amitriptyline, and cyproheptadine on mono- and polysynaptic reflex potentials are due to the inhibition of descending serotonergic systems through 5-HT(2) receptors in the spinal cord [1, 2].

  • CAS Number: 969-33-5
  • MF: C21H22ClN
  • MW: 323.859
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 440.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 194.5ºC

Apimostinel

Apimostinel is an oral NMDA receptor partial agonist.

  • CAS Number: 1421866-48-9
  • MF: C25H37N5O6
  • MW: 503.591
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 878.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 485.2±34.3 °C

H-Glu(OtBu)-OtBu.HCl

H-Glu(OtBu)-OtBu hydrochloride is a glutamate derivative that can be used for substance P antagonist synthesis[1].

  • CAS Number: 32677-01-3
  • MF: C13H26ClNO4
  • MW: 295.803
  • Catalog: Neurokinin Receptor
  • Density: 1.02g/cm3
  • Boiling Point: 311.1ºC at 760 mmHg
  • Melting Point: 60 to 75ºC
  • Flash Point: 78.1ºC

PF-04781340

A potent, selective, CNS penetrant 5-HT2C receptor agonist with Ki of 3 nM and EC50 of 9 nM, without significant P-gp efflux liability; displays >150-fold selectivity over 5-HT2B receptors agonism (EC50=1484 nM); exhibits good metabolic stability in human liver microsomes (HLM) and moderate to good passive permeability in RRCK cells.

  • CAS Number: 1648726-56-0
  • MF: C17H21N3
  • MW: 267.376
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sultopride

Sultopride is a selective antagonist of dopamine D2 receptor.

  • CAS Number: 53583-79-2
  • MF: C17H26N2O4S
  • MW: 354.46400
  • Catalog: Dopamine Receptor
  • Density: 1.16g/cm3
  • Boiling Point: 530ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 274.3ºC

Tanshinone IIA anhydride

Tanshinone IIA anhydride is a potent and irreversible human carboxylesterase (CE) inhibitor with Ki values of 1.9 nM and 1.4 nM for human CE1 and the human intestinal CE (hiCE), respectively[1].

  • CAS Number: 61077-78-9
  • MF: C19H18O4
  • MW: 310.34
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DSP-1053

DSP-1053 is a novel potent serotonin reuptake (SERT) inhibitor with 5-HT1A partial agonistic activity that binds to human serotonin transporter and 5-HT1A receptor with Ki of 1.02 and 5.05 nM, respectively; inhibits serotonin transporter with IC50 of 2.74 nM and shows an intrinsic activity for 5-HT1A receptors of 70.0%; dose-dependently increases extracellular 5-HT levels in rat microdialysis at 3-10 mg/kg, demonstrates antidepressant-like effect in vivo. Depression Phase 1 Discontinued

  • CAS Number: 1176326-78-5
  • MF: C32H38BrNO7S
  • MW: 660.62
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TMPPAA

TMPPAA is an allosteric agonist and positive allosteric modulator of the 5-HT3 receptor. TMPPAA enhances 5-HT-mediated 5-HT3AR signaling[1].

  • CAS Number: 844900-50-1
  • MF: C15H21NO2
  • MW: 247.33
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TRV130 (Racemate)

Oliceridine Racemate (TRV130 Racemate) is the racemate of Oliceridine. Oliceridine is a novel mu opioid receptor (MOR) agonist that preferentially activates G-protein versus β-arrestin signaling pathways coupled to MORs.

  • CAS Number: 1401028-25-8
  • MF: C22H30N2O2S
  • MW: 386.55100
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UBP 310

UBP310 is a selective GluR5 antagonist, with a Kd of 130 nM[1].

  • CAS Number: 902464-46-4
  • MF: C14H15N3O6S
  • MW: 353.35000
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CJ 033466

CJ033466 is a novel and selective 5-HT4 receptor partial agonist with an EC50 of 9 nM and has gastroprokinetic effect[1].

  • CAS Number: 519148-48-2
  • MF: C19H28ClN5O
  • MW: 377.91200
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acephate-d3

Acephate-d3 is the deuterium labeled Acephate. Acephate is an anticholinesterase insecticide that produces cholinotoxicity. Acephate displays weak inhibition of rat AChE but potently inhibits cockroach AChE.

  • CAS Number: 2140327-70-2
  • MF: C4H7D3NO3PS
  • MW: 186.18
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α-Conotoxin MI trifluoroacetate salt

α-Conotoxin M I is a potent and selective inhibitor of mAChR and α1β1γδ nAChR, but has no effect on nicotine-stimulated dopamine release. α-Conotoxins are small, disulfide-rich peptides that competitively inhibit muscle and neuronal nicotinic AChRs[1][2].

  • CAS Number: 88217-10-1
  • MF: C58H88N22O17S4
  • MW: 1493.72000
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ubrogepant

Ubrogepant (MK-1602) is a novel oral calcitonin gene-related peptide receptor (CGRP) antagonist in development for acute treatment of migraine[1].

  • CAS Number: 1374248-77-7
  • MF: C29H26F3N5O3
  • MW: 549.54400
  • Catalog: CGRP Receptor
  • Density: 1.45±0.1 g/cm3(Predicted)
  • Boiling Point: 729.4±60.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

AMPA Receptor Modulator-1

AMPA Receptor Modulator is a potent, oral active and selective AMPAR regulatory protein TARP γ-8 negative modulator with a pIC50 of 9.7, more selective over GluA1/γ-2 (pIC50=5)[1].

  • CAS Number: 2036074-41-4
  • MF: C16H11ClF3NO2
  • MW: 341.71
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PPPA

PPPA is a competitive NMDA receptor antagonist that displays moderate selectivity for NR2A-containing receptors[1][2].

  • CAS Number: 113190-92-4
  • MF: C9H18NO5P
  • MW: 251.21700
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FK 888

FK888 is a potent, selective, and high affinity dipeptide NK1 receptor antagonist. FK888 displaces [3H]-SP binding with a Ki value of 0.69 nM and 0.45 microM. FK888 also inhibits SP-induced airway oedema in guinea-pig after both intravenous and oral administration[1].

  • CAS Number: 138449-07-7
  • MF: C36H36N4O4
  • MW: 588.70
  • Catalog: Neurokinin Receptor
  • Density: 1.26g/cm3
  • Boiling Point: 901.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 499.2ºC