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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DETQ

A novel potent, selective, allosteric and orally active dopamine D1 receptor potentiator with Kb of 26 nM; induces a 21-fold leftward shift in the cAMP response to dopamine in HEK293 cells, 30-fold less potent at rat and mouse D1 receptors and is inactive at the human D5 receptor; robustly (∼10-fold) increases locomotor activity in habituated hD1 mice (3-20 mg/kg), also acts synergistically with L-DOPA to reverse the strong hypokinesia caused by reserpine.

  • CAS Number: 1638667-81-8
  • MF: C22H25Cl2NO3
  • MW: 422.346
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Arachidonoyl-γ-aminobutyric acid

N-Arachidonoyl-GABA is one member of a new class of lipoamino acids related to anandamide identified in bovine brain. N-Arachidonoyl-GABA displays analgesic activity[1].

  • CAS Number: 128201-89-8
  • MF: C24H39NO3
  • MW: 389.571
  • Catalog: GABA Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 580.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 305.1±30.1 °C

NS3861

NS3861 is an agonist of nicotinic acetylcholine receptors (nAChRs) and binds with high affinity to heteromeric α3β4 nAChR. The binding Ki values of 0.62, 25, 7.8, 55 nM for α3β4, α3β2, α4β4, α4β2, respectively[1].

  • CAS Number: 216853-59-7
  • MF: C12H14BrNS
  • MW: 284.22
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Naloxone

Naloxone is an antagonist of Opioid receptor. Naloxone alleviates opioid-overdose-induced respiratory depression. Naloxone may cause pulmonary edema and cardiac arrhythmias[1].

  • CAS Number: 465-65-6
  • MF: C19H21NO4
  • MW: 327.37
  • Catalog: Opioid Receptor
  • Density: 1.43 g/cm3
  • Boiling Point: 532.8ºC at 760 mmHg
  • Melting Point: 184ºC
  • Flash Point: 276.1ºC

SKF 38393 hydrobromide

SKF 38393 hydrobromide is a selective agonist of the dopamine D1 receptor (D1DR) with an IC50 of 110 nM[1].

  • CAS Number: 20012-10-6
  • MF: C16H18BrNO2
  • MW: 336.22400
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DPDPE TFA

DPDPE TFA, an opioid peptide, is a selective δ-opioid receptor (DOR) agonist with anticonvulsant effects[1].

  • CAS Number: 172888-59-4
  • MF: C30H39N5O7S2
  • MW: 645.79
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-HT3 antagonist 1

5-HT3 antagonist 1 is a potent and selective antagonist of serotonin 3 (5-HT3) receptor.

  • CAS Number: 129294-09-3
  • MF: C22H27N5O
  • MW: 377.48300
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Remoxipride hydrochloride

(S)-Remoxipride ((-)-Remoxipride) hydrochloride is a selective dopamine D2-receptor antagonist with an IC50 value of 1.57 μM. (S)-Remoxipride hydrochloride can be used for the research of psychotic disorder[1].

  • CAS Number: 73220-03-8
  • MF: C16H24BrClN2O3
  • MW: 407.73
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Quetiapine hemifumarate-d8

Quetiapine (hemifumarate)-d8 is the deuterium labeled Quetiapine hemifumarate[1]. Quetiapine hemifumarate is a 5-HT receptors agonist with a pEC50 of 4.77 for human 5-HT1A receptor. Quetiapine hemifumarate is a dopamine receptor antagonist with a pIC50 of 6.33 for human D2 receptor. Quetiapine hemifumarate has moderate to high affinity for the human D2, HT1A, 5-HT2A, 5-HT2C receptor with pKis of 7.25, 5.74, 7.54, 5.55. Antidepressant and anxiolytic effects[2].

  • CAS Number: 1435938-24-1
  • MF: (C21D8H17N3O2S)2·C4H4O4
  • MW: 899.18
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Irampanel

Irampanel (BIIR 561) is an AMPA receptor and voltage-dependent sodium channel blocker. Irampanel inhibits kainate-induced currents in rat cortical neurons[1].

  • CAS Number: 206260-33-5
  • MF: C18H19N3O2
  • MW: 309.36200
  • Catalog: iGluR
  • Density: 1.145g/cm3
  • Boiling Point: 471.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 238.9ºC

PEPA

PEPA is an allosteric modulator of AMPA receptors; binds to the GluA2o and GluA3o LBDs and can be utilized as an indicator of AMPA receptor heterogeneity.IC50 value:Target: AMPAR modulatorin vitro: PEPA dose-dependently potentiated AMPA-induced increase of [Ca2+]i. In 90% (72 out of 80) of the cells in which cyclothiazide acts, PEPA potentiated the increased [Ca2+]i induced by AMPA with pronounced cell-to-cell variation in rat hippocampal cultures [1]. PEPA bound to the binding domains of the GluA2 and GluA3 flop isoforms of AMPA receptors [2]. coapplication of AMPA with PEPA protected hippocampal CA1 neurons from brain ischemia-induced death. Coapplication of AMPA with PEPA could prevent downregulated expression of GluR2 subunit caused by ischemia and increase BDNF expression via Lyn-ERK1/2-CREB signaling [4].in vivo: PEPA (3, 10, 30mg/kg body weight) or vehicle was intraperitoneally administered into stressed mice once before the first extinction session. The significant decrease of the freezing response in the extinction sessions was only seen in the 30mg/kg PEPA-administered stressed mice, compared with vehicle-administered stressed mice [3].

  • CAS Number: 141286-78-4
  • MF: C16H16F2N2O4S2
  • MW: 402.43600
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tarafenacin

Tarafenacin(SVT-40776) is a highly selective M3 muscarinic receptor antagonist (Ki= 0.19 nM), ~200 fold selectivity over M2 receptor.IC50 value: 0.19 nM (Ki) [1]Target: M3 muscarinic receptorin vitro: SVT-40776 is highly selective for M(3) over M(2) receptors (Ki = 0.19 nmol.L(-1) for M(3) receptor affinity). SVT-40776 was the most potent in inhibiting carbachol-induced bladder contractions of the anti-cholinergic agents tested, without affecting atrial contractions over the same range of concentrations. SVT-40776 exhibited the highest urinary versus cardiac selectivity (199-fold) [1]. SVT-40776 has a much higher binding affinity (K(d) = 0.4 nM) to M5 mAChR than that of solifenacin (K(d) = 31 nM) with the same reeptor. The calculated binding free energy change (-2.3 ± 0.3 kcal/mol) from solifenacin to SVT-40776 is in good agreement with the experimentally derived binding free energy change (-2.58 kcal/mol), suggesting that our modeled M5 mAChR structure and its complexes with the antagonists are reliable [2].in vivo: In the guinea pig in vivo model, SVT-40776 inhibited 25% of spontaneous bladder contractions at a very low dose (6.97 microg.kg(-1) i.v), without affecting arterial blood pressure [1].

  • CAS Number: 385367-47-5
  • MF: C21H20F4N2O2
  • MW: 408.389
  • Catalog: mAChR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 483.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 246.2±28.7 °C

2,2,6,6-TETRAMETHYLPIPERIDIN-4-YL HEPTANOATE HYDROCHLORIDE

nAChR-IN-1 (2,2,6,6-Tetramethylpiperidin-4-yl heptanoate) is a tetramethylpiperidine heptanoate, a selective nicotinic acetylcholine receptor (nAChR) inhibitor that inhibits nAChRs lacking α5, α6, or β3 subunits. nAChR-IN-1 has the effect of preventing nerve disorder, can be used for nicotinic acetylcholine receptor dysfunction or neurological disorders research[1].

  • CAS Number: 849461-90-1
  • MF: C16H32ClNO2
  • MW: 305.88400
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: 356.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 169.4ºC

2-[(4-Fluorophenyl)sulfonyl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one

Unifiram (DM232) is acts as a potent cognition enhancer through the activation of the AMPA-mediated neurotransmission system. Unifiram (DM232) has the potential for amnesia prevention and neurodegenerative disorder research[1][2].

  • CAS Number: 272786-64-8
  • MF: C13H15FN2O3S
  • MW: 298.33
  • Catalog: iGluR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 479.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 243.8±31.5 °C

Loxapine-d8 hydrochloride

Loxapine-d8 hydrochloride is the deuterium labeled Loxapine. Loxapine Succinate is a D2DR and D4DR inhibitor, serotonergic receptor antagonist and also a dibenzoxazepine anti-psychotic agent[1][2].

  • CAS Number: 1246820-19-8
  • MF: C18H11Cl2D8N3O
  • MW: 372.31800
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A-437203

A-437203 is a selective D3 receptor antagonist with Ki of 71, 1.6, and 6220 nM for D2, D3, and D4 receptors, respectively.

  • CAS Number: 220519-06-2
  • MF: C20H27F3N6OS
  • MW: 456.52800
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D-Cycloserine

D-Cycloserine is an analog of the amino acid D-alanine.Target: AntibacterialD-Cycloserine selectively potentiated the duration of motor cortical excitability enhancements induced by anodal tDCS. D-Cycloserine alone did not modulate excitability [1]. Participants receiving d-cycloserine in addition to exposure therapy reported significantly less social anxiety compared with patients receiving exposure therapy plus placebo. Controlled effect sizes were in the medium to large range [2]. Chronic D-cycloserine significantly reduced nicotine self-administration selectively in rats with low baseline nicotine use, but was ineffective with the rats with higher levels of baseline nicotine self-administration [3].

  • CAS Number: 68-41-7
  • MF: C3H6N2O2
  • MW: 102.092
  • Catalog: Bacterial
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 267ºC
  • Melting Point: 147ºC
  • Flash Point: N/A

2-NAPHTHALENAMINE, 1,2,3,4-TETRAHYDRO-N-2-PROPYNYL-, HYDROCHLORIDE

2-PAT, an analogue of Rasagiline and Selegiline, a reversible MAO-A inhibitor with an IC50 of 0.721 µM. 2-PAT is an inactivator of MAO-B with an IC50 of 14.6 µM. 2-PAT has the potential for Parkinson’s disease and depression research[1].

  • CAS Number: 134467-58-6
  • MF: C13H16ClN
  • MW: 221.726
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cimetropium bromide

Cimetropium Bromide is a mAChR antagonist for long-term treatment of irritable bowel syndrome.

  • CAS Number: 51598-60-8
  • MF: C21H28BrNO4
  • MW: 438.35500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D-Ala-Gly-Phe-Met-NH2

D-Ala-Gly-Phe-Met-NH2, an opioid peptide, is a potent opiate δ-receptor agonist[1].

  • CAS Number: 82948-89-8
  • MF: C19H29N5O4S
  • MW: 423.53
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S 14506 hydrochloride

S-14506 hydrochloride is a potent 5-HT1A agonist. S-14506 hydrochloride displays dopamine antagonist properties by blocking dopamine D2 receptors. S-14506 hydrochloride inhibits the in vivo binding of [3H]raclopride in striatum and olfactory bulbs. S-14506 hydrochloride has the potential for the research of anxiolytic agent[1][2].

  • CAS Number: 286369-38-8
  • MF: C24H27ClFN3O2
  • MW: 443.941
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-PD 128,907 HCl

(+)-PD 128907 hydrochloride is a selective dopamine D2/D3 receptor agonist, with Kis of 1.7, 0.84 nM for human and rat D3 receptors, 179, 770 n M for human and rat D3 receptors, respectively.

  • CAS Number: 300576-59-4
  • MF: C14H20ClNO3
  • MW: 285.76700
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 389ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 189ºC

Minaprine (dihydrochloride)

Minaprine 2Hcl is a reversible inhibitor of MAO-A; weakly inhibit acetylcholinesterase; an antidepressant for treatment of depression.

  • CAS Number: 25953-17-7
  • MF: C17H24Cl2N4O
  • MW: 371.30
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: 531.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 275.1ºC

LY2940094

LY2940094 is a potent, selective and orally available nociceptin receptor (NOP) antagonist with an Ki of 0.105 nM.

  • CAS Number: 1307245-86-8
  • MF: C22H23ClF2N4O2S
  • MW: 480.96
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ru-32514

Ru-32514 is an agonist of benzodiazepine receptor.

  • CAS Number: 90807-98-0
  • MF: C18H17N3O2
  • MW: 307.346
  • Catalog: GABA Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Flibanserin hydrochloride

Flibanserin (BIMT-17; BIMT-17BS) hydrochloride is an orally active serotonin 5-HT1A receptor agonist and 5-HT2A receptor antagonist with Ki values of 1 nM and 49 nM, respectively. Flibanserin hydrochloride binds to dopamine D4 receptors with an Ki value of 4-24 nM. Flibanserin hydrochloride shows anti-depression and anti-anxiety effect, can be used to hypoactive sexual desire disorder (HSDD) research[1]-[5].

  • CAS Number: 147359-76-0
  • MF: C20H22ClF3N4O
  • MW: 426.863
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: >225°C (dec.)
  • Flash Point: N/A

Huperzine A

Huperzine A, an active Lycopodium alkaloid extracted from traditional Chinese herb, is a potent, selective and reversible acetylcholinesterase (AChE) inhibitor and has been widely used in China for the treatment of Alzheimer's disease (AD). IC50 value:Target: AChEHuperzine A exhibited protective effects against d-gal-induced hepatotoxicity and inflamm-aging by inhibiting AChE activity and via the activation of the cholinergic anti-inflammatory pathway. The huperzine A mechanism might be involved in the inhibition of DAMPs-mediated NF-κB nuclear localization and activation. Huperzine A is a potential therapeutic agent for Alzheimer's disease.

  • CAS Number: 120786-18-7
  • MF: C15H18N2O
  • MW: 242.316
  • Catalog: AChE
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 505.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 259.2±30.1 °C

Gidazepam

Gidazepam is an agonist of GABA receptor channels (GABA RCs).

  • CAS Number: 129186-29-4
  • MF: C17H15BrN4O2
  • MW: 387.23100
  • Catalog: GABA Receptor
  • Density: 1.58g/cm3
  • Boiling Point: 675.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 362.4ºC

Naluzotan

Naluzotan is a novel, potent, and selective amidosulfonamide 5-HT1A agonist with IC50 and Ki of appr 20 nM and 5.1 nM, used for the treatment of anxiety and depression; Also a weak hERG K+ channel blocker, with IC50 of 3800 nM.

  • CAS Number: 740873-06-7
  • MF: C23H38N4O3S
  • MW: 450.63800
  • Catalog: 5-HT Receptor
  • Density: 1.169
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP-101,606

Traxoprodil (CP101,606) is a potent and selective NMDA antagonist and protect hippocampal neurons with an IC50 of 10 nM.

  • CAS Number: 134234-12-1
  • MF: C20H25NO3
  • MW: 327.417
  • Catalog: iGluR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 534.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 290.3±28.8 °C