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.


Anti-infection >
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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
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RHC-80267

RHC 80267 (U-57908) is a potent and selective inhibitor of diacylglycerol lipase (DAGL) (with IC50 of 4 μM in canine platelets). RHC-80267 inhibits cholinesterase activity with an IC50 of 4 μM, thereby enhancing the relaxation evoked by acetylcholine. RHC 80267 also inhibits COX and the hydrolysis of phosphatidylcholine (PC)[1][2][3][4].

  • CAS Number: 83654-05-1
  • MF: C20H34N4O4
  • MW: 394.508
  • Catalog: mAChR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Metofenazate

Metofenazate is a selective calmodulin inhibitor.

  • CAS Number: 388-51-2
  • MF: C31H36ClN3O5S
  • MW: 598.15300
  • Catalog: CaMK
  • Density: 1.248 g/cm3
  • Boiling Point: 694.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 374ºC

Domperidone

Domperidone is a dopamine blocker and an antidopaminergic reagent.Target: Dopamine ReceptorDomperidone is a useful alternative to metoclopramide for treatment of gastroparesis due to better tolerability. Effectiveness and side-effects from domperidone may be influenced by patient-related factors including polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and domperidone targets [1]. Domperidone is a dopamine D(2) receptor antagonist, which has been used as antiemetic agent in human beings. The percentage recovery of domperidone from wastewater was 95.0%. Celiprolol was used as the internal standard to access the percentage extraction of domperidone from wastewater [2]. Domperidone, a dopamine antagonist that does not easily cross the blood-brain barrier, is considered the gold standard for treating gastrointestinal symptoms in patients with Parkinson's disease (PD) because the risk of developing extrapyramidal adverse effects is considered minimal [3].

  • CAS Number: 57808-66-9
  • MF: C22H24ClN5O2
  • MW: 425.911
  • Catalog: Dopamine Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 723.6±70.0 °C at 760 mmHg
  • Melting Point: 242.5ºC
  • Flash Point: 391.4±35.7 °C

(Rac)-VU 6008667

Rac-VU 6008667 is a selective negative allosteric modulator of muscarinic acetylcholine receptor subtype 5 (M5 NAM) with IC50s of 1.2 μM and 1.6 μM for human M5 and rat M5, respectively. Rac-VU 6008667 has high CNS penetration[1].

  • CAS Number: 2092917-63-8
  • MF: C24H17ClF2N2O2
  • MW: 438.85
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fluphenazine decanoate dihydrochloride

Fluphenazine decanoate dihydrochloride is a dopamine D2 receptor inhibitor, is a long-acting phenothiazine neuroleptic. Fluphenazine can be used for schizophrenia research[1][2][3].

  • CAS Number: 2376-65-0
  • MF: C32H46Cl2F3N3O2S
  • MW: 664.693
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosnetupitant chloride monohydrochloride

Fosnetupitant chloride monohydrochloride (Pronetupitant chloride monohydrochloride) is an NK1 antagonist with pKi values of 9.5, 6.1 for human NK1 and NK3 receptor, respectively. Fosnetupitant chloride monohydrochloride is a methylene phosphate prodrug of Netupitant[1].

  • CAS Number: 1643757-72-5
  • MF: C31H37Cl2F6N4O5P
  • MW: 761.52
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MAO-B-IN-8

MAO-B-IN-8 is a potent reversible MAO-B inhibitor and an inhibitor of microglial production of neuroinflammatory mediator. MAO-B-IN-8 can be used for neurodegenerative disease research[1].

  • CAS Number: 1638956-60-1
  • MF: C18H16O6
  • MW: 328.32
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAK-071

TAK-071 is a novel muscarinic acetylcholine receptor 1 (M1R) positive allosteric modulator. EC50 of TAK-071 M1R agonist activities is 520 nM[1].

  • CAS Number: 1820812-16-5
  • MF: C24H24FN3O3
  • MW: 421.46
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Latrepirdine

Latrepirdine dihydrochloride is a neuroactive compound with antagonist activity at histaminergic, α-adrenergic, and serotonergic receptors. Latrepirdine stimulates amyloid precursor protein (APP) catabolism and amyloid-β (Aβ) secretion.

  • CAS Number: 97657-92-6
  • MF: C21H27Cl2N3
  • MW: 392.365
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Calmidazolium chloride

Calmidazolium chloride (R 24571) is a calmodulin (CaMK) antagonist, antagonizing CaM-dependent phosphodiesterase and calmodulin-induced activation of erythrocyte Ca2+-transporting ATPase with IC50s of 0.15 and 0.35 μM, respectively[1]. Also in anti-cancer research[2]. Calmidazolium binds to CaMK with a Kd of 3 nM.

  • CAS Number: 57265-65-3
  • MF: C31H23Cl7N2O
  • MW: 687.698
  • Catalog: CaMK
  • Density: N/A
  • Boiling Point: 724.9ºC at 760mmHg
  • Melting Point: 172-176ºC
  • Flash Point: N/A

Ditryptophenaline

Ditryptophenaline ((-)-Ditryptophenaline) is the metabolites of Aspergillus flavus. Ditryptophenaline inhibits substance P receptor and has anti-inflammatory activity[1].

  • CAS Number: 64947-43-9
  • MF: C42H40N6O4
  • MW: 692.80500
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BULBOCAPNINE HYDROCHLORIDE

Bulbocapnine hydrochloride, an aporphine alkaloid, is a dopamine receptor inhibitor. Bulbocapnine hydrochloride inhibits dopamine synthesis. Bulbocapnine hydrochloride also has neuroleptic-like, anticonvulsant and antinociceptive effects[1][2][3].

  • CAS Number: 632-47-3
  • MF: C19H20ClNO4
  • MW: 361.82
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 504ºC at 760 mmHg
  • Melting Point: 209-210ºC
  • Flash Point: 258.6ºC

17-PA

17-PA is a selective antagonist of neurosteroid potentiation and direct gating of GABAA receptors[1].

  • CAS Number: 694438-95-4
  • MF: C25H34O6
  • MW: 430.534
  • Catalog: GABA Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 599.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 201.8±23.6 °C

(+)-Corynoline

Corynoline, isolated from Corydalis incise (Papaveraceae), is a reversible and noncompetitive acetylcholinesterase (AChE) inhibitor with an IC50 of 30.6 μM[1]. Corynoline exhibits anti-inflammatory activity by activating Nrf2[2].

  • CAS Number: 18797-79-0
  • MF: C21H21NO5
  • MW: 367.395
  • Catalog: AChE
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 504.2±50.0 °C at 760 mmHg
  • Melting Point: 217-218ºC
  • Flash Point: 258.7±30.1 °C

Cevimeline hydrochloride hemihydrate

Cevimeline hydrochloride hemihydrate, a novel muscarinic receptor agonist, is a candidate therapeutic drug for xerostomia in Sjogren's syndrome. IC50 value:Target: mAChRThe general pharmacol. properties of this drug on the gastrointestinal, urinary, and reproductive systems and other tissues were investigated in mice, rats, guinea pigs, rabbits, and dogs. The in vitro metab. of SNI-2011 was also evaluated with rat and dog liver microsomes. After oral administration, plasma concns. of SNI-2011 reached to Cmax within 1 h in both species, suggesting that SNI-2011 was quickly absorbed, and then decreased with a t1/2 of 0.4-1.1 h. The bioavailability was 50% and 30% in rats and dogs, resp. Major metabolites in plasma were both S- and N-oxidized metabolites in rats and only N-oxidized metabolite in dogs, indicating that a large species difference was obsd. in the metab. of SNI-2011. Sex difference was also obsd. in the pharmacokinetics of SNI-2011 in rats, but not in dogs. In the in vitro study, chem. inhibition and pH-dependent studies revealed that the sulfoxidn. and N-oxidn. of SNI-2011 were mediated by cytochrome P 450 (CYP) and flavin-contg. monooxygenase (FMO), resp., in both species. In addn., CYP2D and CYP3A were mainly responsible for the sulfoxidn. in rat liver microsomes.

  • CAS Number: 153504-70-2
  • MF: C20H35ClN2O2S2
  • MW: 435.09
  • Catalog: mAChR
  • Density: 1.19g/cm3
  • Boiling Point: 308.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 140.4ºC

BF-168

BF-168, a candidate probe for PET, is found to specifically recognize both neuritic and diffuse plaques, with a Ki of 6.4 nM for Aβ1-42.

  • CAS Number: 634911-47-0
  • MF: C18H17FN2O2
  • MW: 312.34
  • Catalog: Amyloid-β
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Brexpiprazole

Brexpiprazole is a partial agonist of human 5-HT1A and dopamine receptor with Kis of 0.12 nM and 0.3 nM, respectively. Brexpiprazole is also a 5-HT2A receptor antagonist with a Ki of 0.47 nM.

  • CAS Number: 913611-97-9
  • MF: C25H27N3O2S
  • MW: 433.566
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 675.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.1±31.5 °C

Centanafadine Hydrochloride

Centanafadine is dual norepinephrine (NE)/dopamine (DA) transporter inhibitor, also inhibits serotonin transporter, with IC50s of 6 nM, 38 nM and 83 nM for human NE, DA and serotonin transporter , respectively.

  • CAS Number: 924012-43-1
  • MF: C15H15N
  • MW: 209.286
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 363.5±11.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 187.3±14.7 °C

Conantokin G

Conantokin G, a 17-amino-acid peptide, is a potent, selective and competitive antagonist of N-methyl-D-aspartate (NMDA) receptors. Conantokin G inhibits NMDA-evoked currents in murine cortical neurons with an IC50 of 480 nM. Conantokin G has neuroprotective properties[1][2].

  • CAS Number: 93438-65-4
  • MF: C88H138N26O44
  • MW: 2264.19000
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AHN 1-055 hydrochloride

AHN 1-055 hydrochloride is a dopamine uptake inhibitor, with an IC50 of 71 nM. AHN 1-055 hydrochloride binds with high affinity to the dopamine transporter (DAT) and may serve as leads for the development of agentia to treat cocaine abuse[1].

  • CAS Number: 202646-03-5
  • MF: C21H24ClF2NO
  • MW: 379.871
  • Catalog: Dopamine Transporter
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB 399885 hydrochloride

SB-399885 hydrochloride is a 5-HT6 receptor antagonist.

  • CAS Number: 402713-81-9
  • MF: C18H22Cl3N3O4S
  • MW: 482.809
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Homocarnosine

Homocarnosine is a dipeptide of γ-aminobutyric acid (GABA) and histidine unique to brain. Homocarnosine is an inhibitory neuromodulator synthesized in the neuron from GABA and exhibiting anticonvulsant effects[1].Homocarnosine has antioxidant and anti-inflammatory actions, prevention of DNA damage, and inhibition of advanced glycation end-product formation[2].

  • CAS Number: 3650-73-5
  • MF: C10H16N4O3
  • MW: 240.25900
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: 646.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 345.1ºC

Paroxetine HCl

Paroxetine hydrochloride is a potent selective serotonin-reuptake inhibitor, commonly prescribed as an antidepressant and has GRK2 inhibitory ability with IC50 of 14 μM.

  • CAS Number: 78246-49-8
  • MF: C19H21ClFNO3
  • MW: 365.826
  • Catalog: Autophagy
  • Density: 1.213 g/cm3
  • Boiling Point: 451.7ºC at 760 mmHg
  • Melting Point: 129-131ºC
  • Flash Point: 227ºC

Gavestinel

Gavestinel (GV 150526) is a selective and potent the glycine site of the NMDA receptor antagonist. Gavestinel has neuroprotectant effects[1].

  • CAS Number: 153436-22-7
  • MF: C18H12Cl2N2O3
  • MW: 375.21
  • Catalog: iGluR
  • Density: 1.561g/cm3
  • Boiling Point: 701.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 377.8ºC

Azemiopsin

Azemiopsin is a potent nicotinic acetylcholine receptor (nAChR) inhibitor with IC50s of 0.18 μM and 22 μM against T. californica nAChR and human α7 nAChR, respectively. Azemiopsin blocks acetylcholine-induced currents in Xenopus oocytes heterologously expressing human muscle-type nAChR[1].

  • CAS Number: 1391936-86-9
  • MF: C118H174N38O26
  • MW: 2540.88
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-chloro-1-[1-[3-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)propyl]piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one maleate

Domperidone (R33812) monomaleate is an orally active and selective dopamine-2 receptor antagonist. Domperidone monomaleate acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine[1].

  • CAS Number: 83898-65-1
  • MF: C26H28ClN5O6
  • MW: 541.98300
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Diclofensine

Diclofensine(Ro-8-4650) is a potent inhibitor of monoamine reuptake, blocking the uptake of dopamine, noradrenaline, and serotonin by rat brain synaptosomes with IC50 values of 0.74, 2.3, and 3.7 nM, respectively.IC50 value:Target: Dopamine reuptake inhibitorThe action of diclofensine on peripheral neuronal adrenergic function was studied through tests of the blood pressure response to NE, tyramine, and phenylephrine (PE). The blood pressure response to NE was enhanced and that to tyramine was decreased by diclofensine, as a result of its inhibitive action on peripheral neuronal amine uptake [2]. Diclofensine, in concentrations of 0.01, 0.1 and 1 microM caused a marked decrease of 3H-DA uptake. In addition, it was unable to stimulate basal endogenous DA release which, on the contrary, was elicited by d-amphetamine in the same concentration (50 microM). On the other hand, diclofensine (50 microM) caused a 3 fold enhancement of K+-evoked DA release [3].

  • CAS Number: 67165-56-4
  • MF: C17H17Cl2NO
  • MW: 322.229
  • Catalog: Dopamine Transporter
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 422.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 209.4±28.7 °C

Decanoic acid-d19

Decanoic acid-d19 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: 88170-22-3
  • MF: C10HD19O2
  • MW: 191.38200
  • Catalog: iGluR
  • Density: 0.991 g/mL at 25ºC
  • Boiling Point: 268-270ºC(lit.)
  • Melting Point: 30-32ºC(lit.)
  • Flash Point: N/A

Abaperidone

Abaperidone is a potent antagonist of 5-HT2A receptor and dopamine D2 receptor with IC50s of 6.2 and 17 nM.

  • CAS Number: 183849-43-6
  • MF: C25H25FN2O5
  • MW: 452.47500
  • Catalog: 5-HT Receptor
  • Density: 1.32g/cm3
  • Boiling Point: 667.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 357.4ºC

metoclopramide hydrochloride

Metoclopramide hydrochloride hydrate is a dopamine D2 antagonist that is used as an antiemetic.IC50 Value:Target: D2 ReceptorMetoclopramide is a dopamine receptor antagonist which has been used for treatment of a variety of gastrointestinal symptoms over the last thirty years. In various countries, metoclopramide is the antiemetic drug of choice in pregnant women. Findings provide reassurance regarding the safety of metoclopramide for the fetus when the drug is given to women to relieve nausea and vomiting during pregnancy. Evidence also supports its use for gastroparesis (poor stomach emptying) and gastroesophageal reflux disease. It appears to bind to dopamine D2 receptors where it is a receptor antagonist, and is also a mixed 5-HT3 receptor antagonist/ 5-HT4 receptor agonist.

  • CAS Number: 54143-57-6
  • MF: C14H25Cl2N3O3
  • MW: 354.27
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 418.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 207ºC