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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SB269652

SB269652 is the first drug-like allosteric modulator of the dopamine D2 receptor (D2R); a new chemical probe that can differentiate D2R monomers from dimers or oligomers depending on the observed pharmacology.IC50 value: 0.2/0.5 nM [1]Target: D3 receptor antagonistSB269,652 potently (low nanomolar range) abolished specific binding of [(3)H]nemanopride and [(3)H]spiperone to Chinese hamster ovary-transfected D(3) receptors when radioligands were used at 0.2 and 0.5 nM, respectively. However, even at high concentrations (5 μM), SB269,652 only submaximally inhibited the specific binding of these radioligands when they were employed at 10-fold higher concentrations. By analogy, although SB269,652 potently blocked D(3) receptor-mediated activation of Gα(i3) and phosphorylation of extracellular-signal-regulated kinase (ERK)1/2, when concentrations of dopamine were increased by 10-fold, from 1 μM to 10 μM, SB269,652 only submaximally inhibited dopamine-induced stimulation of Gα(i3) [1].

  • CAS Number: 215802-15-6
  • MF: C27H30N4O
  • MW: 426.553
  • Catalog: Dopamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 690.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 371.5±31.5 °C

Varenicline (Hydrochloride)

Varenicline Hcl(CP 526555;Champix) is a nicotinic receptor partial agonist; it stimulates nicotine receptors more weakly than nicotine itself does.IC50 value:Target: nAChRVarenicline(CP 526555; Champix; Chantix) is a prescription medication used to treat smoking addiction. As a partial agonist it both reduces cravings for and decreases the pleasurable effects of cigarettes and other tobacco products. Through these mechanisms Varenicline(CP 526555; Champix; Chantix) can assist some patients to quit smoking.

  • CAS Number: 230615-23-3
  • MF: C13H14ClN3
  • MW: 247.723
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-(-)-5-Fluorowillardiine

(S)-(-)-5-Fluorowillardiine is a potent and specific AMPAR agonist.

  • CAS Number: 140187-23-1
  • MF: C7H8FN3O4
  • MW: 217.15500
  • Catalog: iGluR
  • Density: 1.64 g/cm3
  • Boiling Point: N/A
  • Melting Point: 235ºC
  • Flash Point: N/A

YM-58790 free base

YM-58790 free base is a potent antagonist of mAChR. YM-58790 free base binds M1, M2, M3 with Ki values of 28 nM, 260 nM, and 15 nM. YM-58790 free base exhibits potent inhibitory activity on bladder pressuer in reflexly-evoked rhythmic contraction in rats[1].

  • CAS Number: 168830-70-4
  • MF: C27H31N3O2
  • MW: 429.55
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-Bexicaserin

(S)-Bexcaserin (compound 2) is a 5-HT2C receptor agonist with potential for studying obesity and psychiatric-related diseases[1].

  • CAS Number: 2035818-21-2
  • MF: C15H19F2N3O
  • MW: 295.33
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SYM 2081

SYM 2081 is a high-affinity ligand and potent, selective agonist of kainate receptors, inhibits [3H]-kainate binding with an IC50 of 35 nM, almost 3000- and 200-fold selectivity for kainate receptors over AMPA and NMDA receptors respectively[1].

  • CAS Number: 31137-74-3
  • MF: C6H11NO4
  • MW: 161.16
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: 329.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 153ºC

AS 19

AS19 is a potent, selective 5-HT7 receptor agonist with an IC50 value of 0.83 nM and a Ki of 0.6 nM. AS19 is selective for 5-HT7 over 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT5A receptors (Kis = 89.7 nM, 490 nM, 6.6 nM and 98.5 nM, respectively). AS19 enhances memory consolidation and reverses Scopolamine- or Dizocilpine-induced amnesia[1][2][3].

  • CAS Number: 1000578-26-6
  • MF: C18H25N3
  • MW: 283.411
  • Catalog: 5-HT Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 413.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 203.7±28.7 °C

Oleoyl-D-lysine

Oleoyl-D-lysine is a selective Glycine Transporter-2 (GlyT2) inhibitor based on lipid. Oleoyl-D-lysine reverses neuropathic pain in mice, shows antidrowsiness effect on chronic neuropathic pain. Oleoyl-D-lysine is safe and effective without respiratory depression[1].

  • CAS Number: 2240164-55-8
  • MF: C24H46N2O3
  • MW: 410.63
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

69-23-8 (free base)

Fluphenazine dimaleate is a potent, orally active phenothiazine-based dopamine receptor antagonist. Fluphenazine dimaleate blocks neuronal voltage-gated sodium channels. Fluphenazine dimaleate acts primarily through antagonism of postsynaptic dopamine-2 receptors in mesolimbic, nigrostriatal, and tuberoinfundibular neural pathways. Fluphenazine dimaleate can antagonize Methylphenidate-induced stereotyped gnawing and inhibit climbing behaviour in mice. Fluphenazine dimaleate can be used for researching psychosis and painful peripheral neuropathy associated with diabetes and has potential to inhibit SARS-CoV-2[1][2][3][4][6].

  • CAS Number: 3093-66-1
  • MF: C26H30F3N3O5S
  • MW: 553.59400
  • Catalog: SARS-CoV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mirtazapine-d4

Mirtazapine-d4 is deuterium labeled Mirtazapine. Mirtazapine (Org3770) is a potent and orally active noradrenergic and specific serotonergic antidepressant (NaSSA) agent. Mirtazapine is also a 5-HT2, 5-HT3, histamine H1 receptor and α2-adrenoceptor antagonist with pKi values of 8.05, 8.1, 9.3 and 6.95, respectively[1][2].

  • CAS Number: 1215898-55-7
  • MF: C17H15D4N3
  • MW: 269.38
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Palonosetron hydrochloride

Palonosetron Hcl is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV).IC50 Value:Target: 5-HT ReceptorPalonosetron is the most effective of the 5-HT3 antagonists in controlling delayed CINV nausea and vomiting that appear more than 24 hours after the first dose of a course of chemotherapy.

  • CAS Number: 135729-62-3
  • MF: C19H25ClN2O
  • MW: 332.868
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 470.4ºC at 760 mmHg
  • Melting Point: >290ºC
  • Flash Point: 209.5ºC

Metanopirone

Tandospirone (SM-3997) hydrochloride is a potent and selective 5-HT1A receptor partial agonist, with a Ki of 27 nM. Tandospirone hydrochloride has anxiolytic and antidepressant activities. Tandospirone hydrochloride can be used for the research of the central nervous system disorders and the underlying mechanisms[1][2][3].

  • CAS Number: 99095-10-0
  • MF: C21H30ClN5O2
  • MW: 419.94800
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4,4-Diphenylbutylamine hydrochloride

4,4-Diphenylbutylamine shows affinity for the 5-HT2A and H1 receptors with Kis of 2589 and 1670 nM, respectively[1].

  • CAS Number: 22101-90-2
  • MF: C16H20ClN
  • MW: 261.79
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Iodotubercidin

5-Iodotubercidin is a potent adenosine kinase inhibitor with IC50 of 26 nM.

  • CAS Number: 24386-93-4
  • MF: C11H13IN4O4
  • MW: 392.150
  • Catalog: Adenosine Kinase
  • Density: 2.5±0.1 g/cm3
  • Boiling Point: 701.5±60.0 °C at 760 mmHg
  • Melting Point: 216-217ºC dec.
  • Flash Point: 378.0±32.9 °C

Oxantel

Oxantel (CP-14445), a m-oxyphenol derivative of Pyrantel (HY-12641), is a N-subtype AChR agonist. Oxantel is an anthelmintic, with excellent trichuricidal properties[1][2].

  • CAS Number: 36531-26-7
  • MF: C13H16N2O
  • MW: 216.27900
  • Catalog: nAChR
  • Density: 1.09g/cm3
  • Boiling Point: 383.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 185.5ºC

A-381393

A-381393 is a potent, selective, brain penetrate dopamine D4 receptor antagonist, with Kis of 1.5, 1.9 and 1.6 nM for human dopamine D4.4, D4.2, and D4.7 receptor, respectively, >2700-fold selectivity over D1, D2, D3 and D5 dopamine receptors. A-381393 shows moderate affinity for 5-HT2A (Ki, 370 nM)[1].

  • CAS Number: 726174-00-1
  • MF: C20H24N4
  • MW: 320.43
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Clotiapine

Clothiapine, an atypical antipsychotic agent, shares with clozapine its strong antiserotonergic properties[1].

  • CAS Number: 2058-52-8
  • MF: C18H18ClN3S
  • MW: 343.874
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 483.8±55.0 °C at 760 mmHg
  • Melting Point: 121-123℃
  • Flash Point: 246.4±31.5 °C

U 92016A

U92016A hydrochloride is a potent, metabolically stable, orally acitive 5-HT1A receptor agonist with an exceptionally high degree of intrinsic activity[1][2]. U92016A hydrochloride binds with high affinity to human 5-HT1A receptors expressed in Chinese hamster ovary cells (Ki=0.2 nM)[2].

  • CAS Number: 149654-41-1
  • MF: C19H26ClN3
  • MW: 331.88300
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isonipecotic acid-d9

Isonipecotic acid-d9 is the deuterium labeled Isonipecotic acid[1]. Isonipecotic acid is a GABAA receptor partial agonist[2].

  • CAS Number: 1219798-43-2
  • MF: C6H2D9NO2
  • MW: 138.21
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anabase

Anabaseine, an alkaloid, stimulates a wide variety of animal nicotinic acetylcholine receptors (AChRs), especially the neuromuscular receptors and α7 AChRs[1].

  • CAS Number: 3471-05-4
  • MF: C10H12N2
  • MW: 160.22
  • Catalog: nAChR
  • Density: 1.09g/cm3
  • Boiling Point: 263.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 113.4ºC

farampator

Farampator (CX-691;Org24448) is an AMPA receptor positive modulator.

  • CAS Number: 211735-76-1
  • MF: C12H13N3O2
  • MW: 231.251
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 398.3±34.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.7±25.7 °C

UNII:EU52DFC4WJ

N-Methyl-DL-aspartic acid is a glutamate analogue and acts as a potent neuronal excitant. N-Methyl-DL-aspartic acid is a NMDA receptor agonist and can be used for neurological diseases research[1][2].

  • CAS Number: 17833-53-3
  • MF: C5H9NO4
  • MW: 147.129
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 258.2±30.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 110.0±24.6 °C

Palonosetron

Palonosetron is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV).IC50 Value:Target: 5-HT3 ReceptorPalonosetron is the most effective of the 5-HT3 antagonists in controlling delayed CINV nausea and vomiting that appear more than 24 hours after the first dose of a course of chemotherapy.

  • CAS Number: 135729-61-2
  • MF: C19H24N2O
  • MW: 296.407
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 470.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 209.5±21.1 °C

Oxotremorine M iodide

Oxotremorine M iodide is a potent and selective muscarinic acetylcholine receptor (mAChR) agonist. Oxotremorine M iodide potentiates NMDA receptors by muscarinic receptor dependent and independent mechanisms[1].

  • CAS Number: 3854-04-4
  • MF: C11H19IN2O
  • MW: 322.18600
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MLE-4901

Pavinetant (MLE-4901) is a neurokinin-3 receptor (NK3R) antagonist.

  • CAS Number: 941690-55-7
  • MF: C26H25N3O3S
  • MW: 459.56000
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NMDA-IN-2

NMDA-IN-2 (compound 6b), a Procaine derivative, is a NMDA receptor 2B subtype inhibitor[1].

  • CAS Number: 2761731-14-8
  • MF: C15H22N2O3
  • MW: 278.35
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α-Conotoxin MII TFA

α-Conotoxin MII (α-CTxMII), a 16-amino acid peptide from the venom of the marine snail Conus magus, potently blocks nicotinic acetylcholine receptors (nAChRs) composed of α3β2 subunits, with an IC50 of 0.5 nM. α-Conotoxin MII (α-CTxMII) potently blocks β3-containing neuronal nicotinic receptors [1][2][3].

  • CAS Number: 175735-93-0
  • MF: C67H103N23O22S4
  • MW: 1710.94000
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

mGAT-IN-1

mGAT-IN-1 (compound 28) is a potent and non-selective GAT inhibitor. mGAT-IN-1 has a high inhibitory potency toward mGAT3, with an IC50 of 2.5 μM and pIC50 of 5.61[1].

  • CAS Number: 2556833-08-8
  • MF: C28H34ClN3O2S2
  • MW: 544.17
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-hydroxysaclofen

2-Hydroxysaclofen is a potent γ-amino-butyric-acid-B (GABAB) receptor antagonist. 2-Hydroxysaclofen can abolish nicotine-induced hypolocomotor effects and increases the antinociceptive effects. 2-Hydroxysaclofen can stimulate luteinizing hormone (LH) secretion in female rats[1][2][3].

  • CAS Number: 117354-64-0
  • MF: C9H12ClNO4S
  • MW: 265.71400
  • Catalog: GABA Receptor
  • Density: 1.551 g/cm3
  • Boiling Point: N/A
  • Melting Point: 267-269ºC
  • Flash Point: N/A

NLX-204

NLX-204 (NLX204) is a potent, selective, ERK1/2 phosphorylation-preferring serotonin 5 HT1A receptor agonist with pEC50 of 9.37; shows promising pharmacokinetic profile, also robustly stimulates ERK1/2 phosphorylation in rat cortex and showed highly potent (MED=0.16 mg/kg) and efficacious antidepressant-like activity, totally eliminating immobility in the rat Porsolt test.

  • CAS Number: 2170405-10-2
  • MF: C20H22ClF2N3O2
  • MW: 409.862
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A