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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Bethanechol

Bethanechol is a parasympathomimetic choline carbamate that selectively stimulates muscarinic receptors without any effect on nicotinic receptors.Target: muscarinic receptorHyoscine butylbromide concentration dependently reduced muscle contractions, calcium mobilization, and epithelial secretion induced by the muscarinic agonist bethanechol with IC50 values of 429, 121, and 224 nmol L(-1), respectively.[2] Bethanechol presentes significantly improve of salivary parameters. Bethanechol is effective in decreasing the salivary gland damage.[3] Cerebral malakoplakia is a very rare chronic inflammatory disease. Treatment with antibiotic Bethanechol improves symptoms in association with a decrease in the abnormal calcification and enhancement.[4]

  • CAS Number: 674-38-4
  • MF: C7H17N2O2
  • MW: 161.22200
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isonaringin

Isonaringin shows anti-Alzheimer’s activity by inhibiting AChE[1].

  • CAS Number: 108815-81-2
  • MF: C27H32O14
  • MW: 580.53
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rosiridin

Rosiridin, which is isolated from Rhodiola rosea L., inhibits MAO A and MAO B with potential beneficial effect in depression and senile dementia. Rosiridin shows an inhibition of 83.8% against MAO B at 10 μM (pIC50=5.38)[1].

  • CAS Number: 100462-37-1
  • MF: C16H28O7
  • MW: 332.389
  • Catalog: Monoamine Oxidase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 563.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 294.6±30.1 °C

SR17018

SR17018 is an mu-opioid-receptor (MOR) agonist, binding with GTPγS, with an EC50 of 97 nM.

  • CAS Number: 2134602-45-0
  • MF: C19H18Cl3N3O
  • MW: 410.72
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGRP antagonist 2

CGRP antagonist 2 is a CGRP receptor antagonist. CGRP antagonist 2 can be used for pain relief[1].

  • CAS Number: 866086-05-7
  • MF: C35H47N5O6
  • MW: 633.78
  • Catalog: CGRP Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIB-1553A

SIB-1553A hydrochloride is an orally bioavailable nicotinic acetylcholine receptors (nAChRs) agonist, with selectivity for β4 subunit-containing nAChRs. SIB-1553A hydrochloride is also a selective neuronal nAChR ligand. SIB-1553A hydrochloride is a cognitive enhancer, and has therapeutic potential for the symptomatic treatment of Alzheimer’s disease and other cognitive disorders[1][2].

  • CAS Number: 191611-89-9
  • MF: C13H20ClNOS
  • MW: 273.822
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-LSD1 Dihydrochloride

GSK-LSD1 Dihydrochloride is a potent, selective and irreversible lysine specific demethylase 1 (LSD1) inhibitor with an IC50 of 16 nM.

  • CAS Number: 2102933-95-7
  • MF: C14H22Cl2N2
  • MW: 289.24
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Endomorphin-2

Endomorphin 2, a high affinity, highly selective agonist of the μ-opioid receptor, displays reasonable affinities for kappa3 binding sites, with Ki value between 20 and 30 nM.

  • CAS Number: 141801-26-5
  • MF: C32H37N5O5
  • MW: 571.66700
  • Catalog: Peptides
  • Density: 1.292g/cm3
  • Boiling Point: 972.4ºC at 760mmHg
  • Melting Point: 130-131℃
  • Flash Point: 541.9ºC

N'-benzylpivalohydrazide

Pivalylbenzhydrazine (Pivhydrazine) is a potent monoamine oxidase (MAO) inhibitor. Pivalylbenzhydrazine decreases cartilage growth in normal rats. Pivalylbenzhydrazine can be used in research of depression[1].

  • CAS Number: 306-19-4
  • MF: C12H18N2O
  • MW: 206.28400
  • Catalog: Monoamine Oxidase
  • Density: 1.015g/cm3
  • Boiling Point: 296.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 105.6ºC

Venlafaxine-d10 hydrochloride

Venlafaxine-d10 (Wy 45030-d10) is the deuterium labeled Venlafaxine hydrochloride. Venlafaxine (Wy 45030) hydrochloride is an orally active, potent serotonin (5-HT)/norepinephrine (NE) reuptake dual inhibitor. Venlafaxine is an antidepressant[1][2].

  • CAS Number: 1216539-56-8
  • MF: C17H18ClD10NO2
  • MW: 323.92433778
  • Catalog: Serotonin Transporter
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Penconazole-d7

Penconazole-d7 is the deuterium labeled Penconazole[1]. Penconazole is a typical triazole fungicide, and mainly applied on apples, grapes, and vegetables to control powdery mildew. Penconazole inhibits sterol biosynthesis in fungi. Penconazole decrease AChE activity in the cerebrum and cerebellum of rats[2][3].

  • CAS Number: 1628110-84-8
  • MF: C13H8D7CL2N3
  • MW: 291.23
  • Catalog: Fungal
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 415.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 204.9±31.5 °C

PRX933 hydrochloride

PRX933 hydrochloride is a 5-HT2c receptor agonist extracted from patent WO 2014140631 A1.

  • CAS Number: 639029-42-8
  • MF: C16H22ClN5O2
  • MW: 351.83
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(D-Pen2,Pen5)-Enkephalin

[DPen2, Pen5] Enkephalin is a δ-opioid receptor selective analog of [Leu5]-Enkephalin (HY-P0288)[1].

  • CAS Number: 88373-72-2
  • MF: C30H39N5O7S2
  • MW: 645.790
  • Catalog: Opioid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 1038.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 581.9±34.3 °C

β-Endorphin (30-31) (human)

Glycyl-L-glutamic acid is a neurotrophic factor (NF) in vivo, and exerts function of maintenance of AChE content and activity. Glycyl-L-glutamic acid doesn’t act directly on AChE synthesis, and may prevent preganglionic neuronal degeneration[1][2].

  • CAS Number: 7412-78-4
  • MF: C7H12N2O5
  • MW: 204.181
  • Catalog: AChE
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 536.6±50.0 °C at 760 mmHg
  • Melting Point: 155-158ºC (dec.)(lit.)
  • Flash Point: 278.3±30.1 °C

Indalpine

Indalpine (LM 5008) is a potent and selective 5-HT uptake blocker. Indalpine is potent in displacing 3H-5-HT bound to brain membranes with the IC50 of 36 μM[1]. Indalpine, two antidepressant agent[2].

  • CAS Number: 63758-79-2
  • MF: C15H20N2
  • MW: 228.33300
  • Catalog: Serotonin Transporter
  • Density: 1.07 g/cm3
  • Boiling Point: 405.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 198.8ºC

NCS-382

NCS-382 is a potent GABA receptor antagonist and also a GHBR receptor antagonist. NCS-382 has anticonvulsant and antisedative activity. NCS-382 is used in the related research of hereditary nervous system diseases[1][4].

  • CAS Number: 520505-01-5
  • MF: C13H14O3
  • MW: 218.25
  • Catalog: GABA Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 460.8±30.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 246.6±21.1 °C

Loperamide

Loperamide (ADL 2-1294) is a selective μ opioid receptor agonist with Kis of 3, 48 and 1156 nM against μ, δ and κ opioid receptor, respectively. Loperamide can be used as an antidiarrheal agent[1].

  • CAS Number: 53179-11-6
  • MF: C29H33ClN2O2
  • MW: 477.04
  • Catalog: Opioid Receptor
  • Density: 1.187g/cm3
  • Boiling Point: 647.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 345.2ºC

Almotriptan

Almotriptan Malate is a 5-HT1B/1D-receptor agonist used to treat migraine.IC50:Target: 5-hydroxytryptamine1B/1D (5-HT1B/1D) ReceptorAlmotriptan Malate is a selective 5-hydroxytryptamine1B/1D (5-HT1B/1D) receptor agonist, used for the treatment of Migraine attacks in adults. Almotriptan showed low nanomolar affinity for the 5-HT(1B) and 5-HT(1D) receptors in several species, including the human, while affinity for 5-HT receptors other than 5-HT(1B/1D) was clearly less. Almotriptan did not exhibit significant affinity for several non-5-HT receptors studied up to 100 microM. Almotriptan inhibited forskolin-stimulated cyclic AMP accumulation in HeLa cells transfected with 5-HT(1B) or 5-HT(1D) human receptors [1]. Almotriptan had a mild antiemetic effect and a slight, transient diuretic effect in dogs, although the latter effect is probably of no clinical relevance. In addition, no effect on the respiratory system of conscious guinea pigs was observed following almotriptan treatment. These results indicate that almotriptan has a favourable safety profile with respect to the central nervous, renal and respiratory systems [2].

  • CAS Number: 181183-52-8
  • MF: C21H31N3O7S
  • MW: 469.552
  • Catalog: 5-HT Receptor
  • Density: 1.27g/cm3
  • Boiling Point: 538.7ºC at 760mmHg
  • Melting Point: 170-172ºC
  • Flash Point: 279.6ºC

2H-Tetrazole-2-carboxamide, 5-([1,1'-biphenyl]-4-ylmethyl)-N,N-dimethyl

AM6701 is a potent FAAH/MAGL inhibitor (equipotent inhibitory IC50: 1.2 nM) with neuroprotective effects[1].

  • CAS Number: 1010096-65-7
  • MF: C17H17N5O
  • MW: 307.35
  • Catalog: FAAH
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 506.1±53.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 259.9±30.9 °C

PZM-21

PZM21 is a potent and selective μ opioid receptor agonist with an EC50 of 1.8 nM.

  • CAS Number: 1997387-43-5
  • MF: C19H27N3O2S
  • MW: 361.50
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Piromelatine

Piromelatine (Neu-P11) is a melatonin MT1/MT2 receptor agonist, serotonin 5-HT1A/5-HT1D agonist, and serotonin 5-HT2B antagonist. Piromelatine (Neu-P11) possesses sleep promoting, analgesic, anti-neurodegenerative, anxiolytic and antidepressant potentials. Piromelatine (Neu-P11) also possesses pain-related P2X3, TRPV1, and Nav1.7 channel-inhibition capacities[1][2][3].

  • CAS Number: 946846-83-9
  • MF: C17H16N2O4
  • MW: 312.32000
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Xanthohumol I

Xanthohumol I, a chalkone, is a derivative of Xanthohumol (HY-N1067). Xanthohumol is a Cholinesterase (ChE) inhibitor, which inhibits acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) wih IC50s of 71.34 μM and 32.67 μM, respectively. The hydroxy compound of Xanthohumol (3-hydroxy-xanthohumol), also shoes inhibitory effect on AChE and BChE with IC50s of 51.25 μM and 63.07 μM[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Talsaclidine

Talsaclidine is a muscarinic agonist with preferential neuron-stimulating properties. Talsaclidine is a full agonist at the M1 subtype, and as a partial agonist at the M2 and M3 subtypes[1][2][3][4].

  • CAS Number: 147025-53-4
  • MF: C10H15NO
  • MW: 165.23200
  • Catalog: mAChR
  • Density: 1.06g/cm3
  • Boiling Point: 251.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 73.3ºC

MK-8931

Verubecestat (MK-8931) is a beta-secretase 1 (BACE1) inhibitor under investigation for the treatment of Alzheimer's Disease.

  • CAS Number: 1286770-55-5
  • MF: C17H17F2N5O3S
  • MW: 409.410
  • Catalog: Beta-secretase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6,2'-Dihydroxyflavone

6,2'-Dihydroxyflavone is a novel antagonist of GABAA receptor.

  • CAS Number: 92439-20-8
  • MF: C15H10O4
  • MW: 254.23700
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylicacidhydrochloride;SKF89976AHCl

SKF89976A hydrochloride is a selective GABA transporter (GAT-1) inhibitor with IC50s of 0.28 μM, 137.34 μM and 202.8 μM for GAT-1, GAT-2 and GAT-3 in CHO cells, respectively.

  • CAS Number: 85375-15-1
  • MF: C22H26ClNO2
  • MW: 371.90000
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: 531.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 275.2ºC

Benzoctamine Hydrochloride

Benzoctamine hydrochloride (Ba-30803) is a psychoactive agent with anti-anxiety effect. Benzoctamine hydrochloride blocks the central postsynaptic serotonin receptors and decreases 5-HT turnover in the brain[1][2].

  • CAS Number: 10085-81-1
  • MF: C18H20ClN
  • MW: 285.81100
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 372ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 181.1ºC

[Lys5,MeLeu9,Nle10] -NKA(4-10)

[Lys5,MeLeu9,Nle10]-NKA(4-10) is a highly selective and potent NK2 receptor agonist, with an IC50 of 6.1 nM[1].

  • CAS Number: 137565-28-7
  • MF: C39H65N9O9
  • MW: 803.98800
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NGB 2904

NGB 2904 is an orally active and selective dopamine (DA) D3 receptor antagonist. NGB 2904 can be used for the research of cocaine addiction[1].

  • CAS Number: 189060-98-8
  • MF: C28H30Cl3N3O
  • MW: 530.91600
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 708.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.4ºC

SB269970 HCl

SB269970 hydrochloride is a hydrochloride salt form of SB-269970, which is a 5-HT7 receptor antagonist with pKi of 8.3, exhibits >50-fold selectivity against other receptors.IC50 Value: 8.3 (pKi for 5-HT7) [1]Target: 5-HT7 receptorin vitro: 5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes (pEC(50) of 8.4+/-0.2) was inhibited by SB-269970-A (0.3 microM) with a pK(B) (8.3+/-0.1) in good agreement with its antagonist potency at the human cloned 5-HT(7(a)) receptor and its binding affinity at guinea-pig cortical membranes. 5-HT(7) receptor mRNA was highly expressed in human hypothalamus, amygdala, thalamus, hippocampus and testis [1]. Cortical slices were loaded with [(3)H]-5-HT and release was evoked by electrical stimulation. 5-CT inhibited the evoked release of [(3)H]-5-HT in a concentration-dependent manner. SB-269970 had no significant effect on [(3)H]-5-HT release while the 5-HT(1B) receptor antagonist, SB-224289 significantly potentiated [(3)H]-5-HT release. In addition, SB-269970 was unable to attenuate the 5-CT-induced inhibition of release while SB-224289 produced a rightward shift of the 5-CT response, generating estimated pK(B) values of 7.8 and 7.6 at the guinea-pig and rat terminal 5-HT autoreceptors respectively [2].in vivo: Acute administration of SB-269970 (1 mg/kg) or amisulpride (3 mg/kg) ameliorated ketamine-induced cognitive inflexibility and novel object recognition deficit in rats. Both compounds were also effective in attenuating ketamine-evoked disruption of social interactions [3]. Pretreatment with a dose of SB-269970 (0.5 mM) that significantly affects sleep variables antagonized the LP-44 (2.5 mM)-induced suppression of REMS and of the number of REM periods [4].Toxicity: N/AClinical trial: N/A

  • CAS Number: 261901-57-9
  • MF: C18H29ClN2O3S
  • MW: 388.95200
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A