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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Pyrazine,2-chloro-6-(1-piperazinyl)-

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

  • CAS Number: 64022-27-1
  • MF: C4H9NO2
  • MW: 103.120
  • Catalog: 5-HT Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 215.2±23.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 83.9±22.6 °C

Org 12962

Org-12962 is a potent, selective and orally active 5-HT2C receptor agonist with a pEC50 value of 7.01. Org-12962 also exhibits high effacy for the 5-HT2A and 5-HT2B receptor with pEC50s of 6.38 and 6.28, respectively[1][3].Org-12962 displays antiaversive effects in a rat model of panic-like anxiety[2].

  • CAS Number: 132834-56-1
  • MF: C10H11ClF3N3
  • MW: 265.66300
  • Catalog: 5-HT Receptor
  • Density: 1.454g/cm3
  • Boiling Point: 286.004ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 126.771ºC

(β-Ala8)-Neurokinin A (4-10)

(β-Ala8)-Neurokinin A (4-10), a neuropeptide, is a potent and selective NK-2 tachykinin receptor (Neurokinin Receptor) agonist[1].

  • CAS Number: 127633-71-0
  • MF: C35H56N8O9S
  • MW: 764.93200
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY56110

LY56110 is an orally active aromatase inhibitor. LY56110 inhibits P-450-dependent p-nitroanisole O-demethylation and ethylmorphine N-demethylation in hepatic microsomes isolated from rat, with the IC50 of 2.5 and 11 μΜ, respectively. LY56110 can be used for neurological disorder study[1][2].

  • CAS Number: 26766-37-0
  • MF: C17H12Cl2N2
  • MW: 315.20
  • Catalog: Cytochrome P450
  • Density: 1.296g/cm3
  • Boiling Point: 438.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 251.5ºC

Trimebutine

Trimebutine is a drug with antimuscarinic and weak mu opioid agonist effects.Target: Opioid ReceptorTrimebutine is an agonist of peripheral mu, kappa and delta opiate receptors, used as spasmolytic agent for treatment of both acute and chronic abdominal pain [1]. The major product from drug metabolism of trimebutine in human beings is nor-trimebutine, which comes from removal of one of the methyl groups attached to nitrogen. Trimebutine exerts its effects in part due to causing a premature activation of phase III of the migrating motor complex in the digestive tract [2, 3].

  • CAS Number: 39133-31-8
  • MF: C22H29NO5
  • MW: 387.469
  • Catalog: Opioid Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 457.9±34.0 °C at 760 mmHg
  • Melting Point: 79ºC
  • Flash Point: 230.8±25.7 °C

Galantamine hydrobromide

Galanthamine hydrobromide is a long-acting, centrally active acetylcholinesterase(AChE) inhibitor (IC50 = 410 nM) and allosteric potentiator at neuronal nicotinic ACh receptors. IC50 Value: 410 nM Target: AChEGalanthamine hydrobromide prevents β-amyloid-induced apoptosis in SH-SY5Y and bovine chromaffin cells. Long-term administration reduces amyloid precursor protein deposition and neurodegeneration in a mouse model of Alzheimer's disease.

  • CAS Number: 1953-04-4
  • MF: C17H22BrNO3
  • MW: 368.266
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 256 °C
  • Flash Point: N/A

Org 12962 HCl

Org 12962 hydrochloride is a potent, selective and efficacious 5-HT2C receptor agonist and exhibits pEC50 values of 7.01, 6.38 and 6.28 for 5-HT2C, 5-HT2A and 5-HT2A, respectively. Org 12962 hydrochloride is effective in panic-like anxiety animal model[2].

  • CAS Number: 210821-63-9
  • MF: C10H12Cl2F3N3
  • MW: 302.12400
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 387.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 187.9ºC

Ondansetron Hydrochloride

Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly as anantiemetic (to treat nausea and vomiting), often following chemotherapy.Target: 5- HT ReceptorIC50 Value: in vitro: 5-HT evoked transient inward currents (EC50 = 3.4 microM; Hill coefficient = 1.8) that were blocked by the 5-HT3 receptor antagonist ondansetron (IC50 = 103 pM) [1]. The 5-HT3A receptor antagonist ondansetron (0.3 nM) reversibly inhibited the 5-HT (30 microM) signal by 70% and at 3 nM it abolished the response [2].in vivo: Acute ondansetron administration at the lowest dose (0.1 mg/kg, IP) tested had no effect, while other doses (0.33 and 1 mg/kg, IP) produced improvements in auditory gating [3]. Different doses of ondansetron were injected intraperitoneally (i.p.) at fixed times during the day to determine both the sublethal (TD50) and lethal (LD50) doses, which were, respectively, 3.7 +/- 0.6 mg/kg and 4.6 +/- 0.5 mg/kg [4]. ondansetron (0.25-1.0 mg/kg, subcutaneously) given before the challenge dose of ethanol (2.4 g/kg, intraperitoneally) injection, significantly and dose dependently attenuated the expression of sensitization. In addition, ondansetron (1.0 mg/kg, subcutaneously) given before ethanol injection on days 1, 4, 7, and 10 significantly blocked the development (days 1, 4, 7, and 10), and expression (day 15) of sensitization to the locomotor stimulant effect of ethanol injection [5]. Toxicity: Ondansetron may be safe in lower doses used to prevent nausea and vomiting in radiation treatment or postoperatively. However, as there is a report that a lower dose of ondansetron prolonged the QT interval in healthy volunteers, this needs to be clarified by the FDA [6].

  • CAS Number: 99614-01-4
  • MF: C18H20ClN3O
  • MW: 329.824
  • Catalog: 5-HT Receptor
  • Density: 1.27g/cm3
  • Boiling Point: 546ºC at 760mmHg
  • Melting Point: 178.5-179.5ºC
  • Flash Point: 284ºC

Syntide 2 trifluoroacetate salt

Syntide 2 is recognized as a substrate by Ca2+/calmodulin-dependent protein kinase II (CaMKII) with a Ki of 12 μM.

  • CAS Number: 108334-68-5
  • MF: C68H122N20O18
  • MW: 1507.82000
  • Catalog: Peptides
  • Density: 1.4 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CIMOXATONE

Cimoxatone (MD 780515) is a reversible, selectively and orally active type A monoamine oxidase (MAO-A) inhibitor. Cimoxatone enhances the anorectic action of Serotonin (HY-B1473A)[1].

  • CAS Number: 73815-11-9
  • MF: C19H18N2O4
  • MW: 338.35700
  • Catalog: Monoamine Oxidase
  • Density: 1.29g/cm3
  • Boiling Point: 509.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 261.8ºC

SKF 82958 hydrobromide

SKF 82958 hydrobromide is a D1/D5 receptor full agonist. IC50 value:Target: D1/D5 receptorin vitro: Neuropeptide and immediate early gene expression in striatonigral neurons of the normosensitive striatum is induced by mixed D1 receptor SKF-82958, which induces behavioral activity and preprodynorphin (PPD) and substance P (SP) gene expression in medium spiny neurons in the dorsal, and especially, in the ventral striatum. in vivo:Quantitative in situ hybridization was used to examine the contribution of muscarinic receptors to the transynaptic regulation of striatal gene expression induced by D1receptor activation. The acute injection of the full D1 agonist, SKF-82958, would induce PPD, SP and PPE mRNA expression in the intact rat striatum.

  • CAS Number: 74115-01-8
  • MF: C19H21BrClNO2
  • MW: 410.73300
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IC 87201

IC87201, an inhibitor of PSD95-nNOS protein-protein interactions, suppresses NMDAR-dependent NO and cGMP formation.

  • CAS Number: 866927-10-8
  • MF: C13H10Cl2N4O
  • MW: 309.151
  • Catalog: iGluR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 525.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 271.3±32.9 °C

Dynorphin A trifluoroacetate salt

Dynorphin A, an endogenous opioid peptide, is a highy potent kappa opioid receptor (KOR) activator. Dynorphin A also serve as an agonist for other opioid receptors,  such as mu (MOR) and delta (DOR)[1].

  • CAS Number: 80448-90-4
  • MF: C99H155N31O23
  • MW: 2147.484
  • Catalog: Opioid Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aloveroside A

Aloveroside A is a triglucosylnaphthalene derivative isolated from ethanolic extract of aloe vera. Aloveroside A has weak bACE inhibitory activity (inhibition rate at a dose of 100 μg/mL is approximately 18.68%)[1].

  • CAS Number: 1246930-65-3
  • MF: C30H40O17
  • MW: 672.63
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ETAP

ETAP is a MAO-A and MAO-B inhibitor. ETAP has antidepressant-like effect. ETAP can be used for research of major depressive disorder[1].

  • CAS Number: 2575731-47-2
  • MF: C18H17N3O
  • MW: 291.35
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Org-26576

Org 26576 is a AMPA receptor positive allosteric modulator.

  • CAS Number: 1026791-61-6
  • MF: C11H12N2O2
  • MW: 204.22500
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Corynoxidine

(-)-Corynoxidine is an acetylcholinesterase inhibitor with an IC50 value of 89.0 μM, isolated from the aerial parts of Corydalis speciosa[1].(-)-Corynoxidine exhibits antibacterial activities against Staphylococcus aureus and methicillin-resistant S. aureus strains in different degrees[2].

  • CAS Number: 57906-85-1
  • MF: C21H25NO5
  • MW: 371.42700
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Opiranserin hydrochloride

Opiranserin (VVZ-149) hydrochloride, a non-opioid and non-NSAID analgesic candidate, is a dual antagonist of glycine transporter type 2 (GlyT2) and serotonin receptor 2A (5HT2A), with IC50s of 0.86 and 1.3 μM, respectively. Opiranserin hydrochloride shows antagonistic activity on rP2X3 (IC50=0.87 μM). Opiranserin hydrochloride is development as an injectable agent for the treatment of postoperative pain[1][2][3].

  • CAS Number: 1440796-75-7
  • MF: C21H35ClN2O5
  • MW: 430.97
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Indole-2-carboxylic acid

Indole-2-carboxylic acid is a strong inhibitor of lipid peroxidation. Indole-2-carboxylic acid (I2CA) specifically and competitively inhibits the potentiation by glycine of NMDA-gated current[1][2].

  • CAS Number: 1477-50-5
  • MF: C9H7NO2
  • MW: 161.157
  • Catalog: iGluR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 419.6±18.0 °C at 760 mmHg
  • Melting Point: 202-206 °C(lit.)
  • Flash Point: 207.6±21.2 °C

Milnacipran ((1S-cis) hydrochloride)

Milnacipran (1S-cis) hydrochloride is a serotonin-norepinephrine reuptake inhibitor (SNRI), used in the clinical treatment of fibromyalgia.

  • CAS Number: 175131-60-9
  • MF: C15H23ClN2O
  • MW: 282.81
  • Catalog: Serotonin Transporter
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nialamide

Nialamide is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class that was used as an antidepressant.

  • CAS Number: 51-12-7
  • MF: C16H18N4O2
  • MW: 298.34000
  • Catalog: MCHR1 (GPR24)
  • Density: 1.203g/cm3
  • Boiling Point: 538.1ºC at 760mmHg
  • Melting Point: 152-154ºC(lit.)
  • Flash Point: 279.2ºC

Flunarizine

Flunarizine is a potent dual Na+/Ca2+ channel (T-type) blocker. Flunarizine is a D2 dopamine receptor antagonist. Flunarizine shows anticonvulsive and antimigraine activity, and peripheral vasodilator effects[1][2][3][4][5].

  • CAS Number: 52468-60-7
  • MF: C26H26F2N2
  • MW: 404.49500
  • Catalog: Dopamine Receptor
  • Density: 1.17 g/cm3
  • Boiling Point: 511.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: N/A

Alniditan

Alniditan is a potent 5-HT1B/1D receptors agonist, with IC50 of 1.7 and 1.3 nM in HEK 293 cells, and pKi value of 8.96 and 9.40 for 5-HT1B/1D receptors, respectively.

  • CAS Number: 152317-89-0
  • MF: C17H26N4O
  • MW: 302.41500
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZT 52656A hydrochloride

ZT 52656A is a selective kappa opioid agonist, used for the prevention or alleviation of pain in the eye.

  • CAS Number: 115730-24-0
  • MF: C19H26ClF3N2O
  • MW: 390.87
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Elinzanetant

Elinzanetant is a neurokinin receptors antagonist used for the research of Schizophrenia[1].

  • CAS Number: 929046-33-3
  • MF: C33H35F7N4O3
  • MW: 668.64
  • Catalog: Neurokinin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 672.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 360.3±31.5 °C

β2AR agonist /M-receptor antagonist-1

β2AR agonist /M-receptor antagonist-1 is a potent dual muscarinic antagonist/beta 2 agonist (MABA). β2AR agonist /M-receptor antagonist-1 potently relaxes either Carbachol (HY-B1208)-induced contraction, in the absence (MABA) or presence of Propranolol (M3; HY-B1208), or Histamine (HY-B1204)-induced contraction (β2)[1][2].

  • CAS Number: 2772700-36-2
  • MF: C33H40FN5O5S2
  • MW: 669.83
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Met-Enkephalin acetate salt

Tyr-Gly-Gly-Phe-Met-OH regulates human immune function and inhibits tumor growth via binding to the opioid receptor.

  • CAS Number: 58569-55-4
  • MF: C27H35N5O7S
  • MW: 573.66100
  • Catalog: Peptides
  • Density: 1.324 g/cm3
  • Boiling Point: 1052.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 590.6ºC

Tiagabine

Tiagabine(NO328) is a selective gamma-aminobutyric acid (GABA) reuptake inhibitor.Target: GABA reuptake inhibitorTiagabine had an early onset of effect, as shown by significant reduction from baseline in mean HAM-A total score compared with placebo at week 1 (observed cases, p < .05). Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status. Symptoms of a discontinuation syndrome during taper were not observed. Tiagabine may be a useful treatment option for adult patients diagnosed with GAD [1]. Tiagabine was generally well tolerated; the most common adverse events were nausea, dizziness and headaches [2]. Tiagabine (0.1 microM), an antiepileptic drug that specifically inhibits the GAT-1 GABA transporter inhibited GABA uptake 50% in temporal cortex and 60-68% in white structures [3].

  • CAS Number: 115103-54-3
  • MF: C20H25NO2S2
  • MW: 375.55
  • Catalog: GABA Receptor
  • Density: 1.208 g/cm3
  • Boiling Point: 568ºC at 760 mmHg
  • Melting Point: 192oC dec.
  • Flash Point: 297.3ºC

Salvinorin B Mesylate

Mesyl Salvinorin B is a potent and selective kappa opioid receptor (KOP-r) agonist. Mesyl Salvinorin B prevents the ADE (Alcohol deprivation effect) in mice. Mesyl Salvinorin B dose-dependently reduces alcohol intake and preference in CED (chronic escalation drinking) mice[1][2].

  • CAS Number: 862073-79-8
  • MF: C22H28O9S
  • MW: 468.52
  • Catalog: Opioid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 649.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 346.6±31.5 °C

BRL 15572 hydrochloride

BRL-15572 hydrochloride is a selective antagonist of h5-HT1D, displays high affinity for h5-HT1D receptors. BRL-15572 hydrochloride could be useful pharmacological agents to characterise 5-HT1D receptor mediated responses[1].

  • CAS Number: 1173022-77-9
  • MF: C25H28Cl2N2O
  • MW: 443.409
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A