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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(Rac)-5-Hydroxymethyl Tolterodine

(Rac)-5-Hydroxymethyl Tolterodine ((Rac)-Desfesoterodine), an active metabolite of Tolterodine, is a mAChR antagonist (Ki values of 2.3 nM, 2 nM, 2.5 nM, 2.8 nM, and 2.9 nM for M1, M2, M3, M4, and M5 receptors, respectively). (Rac)-5-Hydroxymethyl Tolterodine can be used for overactive bladder research[1].

  • CAS Number: 200801-70-3
  • MF: C22H31NO2
  • MW: 341.49
  • Catalog: mAChR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 490.7±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.2±27.4 °C

Levomilnacipran

Dextromilnacipran (F2696; (1R,2S)-milnacipran), an enantiomer of milnacipran, is a selective serotonin and norepinephrine (5-HT/NE) reuptake inhibitor. Dextromilnacipran also is a human alpha-adrenergic receptor antagonist, with an IC50 of 3.4 μM. (patent WO2013014263A1).

  • CAS Number: 96847-55-1
  • MF: C15H22N2O
  • MW: 246.34800
  • Catalog: Serotonin Transporter
  • Density: 1.077
  • Boiling Point: 393ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: N/A

Etilevodopa hydrochloride

Etilevodopa (L-Dopa ethyl ester) hydrochloride, an ethyl-ester prodrug of Levodopa, is rapidly hydrolyzed to Levodopa and ethanol by nonspecific esterases in the gastrointestinal tract. Etilevodopa hydrochloride is used for the treatment of Parkinson disease (PD). Levodopa is the direct precursor of dopamine and is a suitable prodrug as it facilitates CNS penetration and delivers dopamine[1][2][3].

  • CAS Number: 39740-30-2
  • MF: C11H16ClNO4
  • MW: 261.70200
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lazabemide

Lazabemide(Ro 19-6327/000) is selective, reversible monoamine oxidase B (MAO-B) inhibitor (IC50 values are 0.03 and > 100 μM for MAO-B and MAO-A respectively).IC50 value: 30 nM [1]Target: MAO-B inhibitorin vitro: The in vitro binding characteristics of both radiolabeled inhibitors revealed them to be selective, high-affinity ligands for the respective enzymes. KD and Bmax values for 3H-Ro 41-1049 in rat cerebral cortex were 10.7 nM and 7.38 pmol/mg protein, respectively, and for 3H-Ro 19-6327 were 18.4 nM and 3.45 pmol/mg protein, respectively [1]. The IC50 values for lazabemide and Ro 16-6491, respectively, were: 86 microM and 90 microM for NA uptake; 123 microM and 90 microM for 5HT uptake; > 500 microM and > 1000 microM for DA uptake. Lazabemide and Ro 16-6491 also differed from L-deprenyl in their ability to induce release of endogenous monoamines from synaptosomes. Thus, Ro 16-6491 (500 microM) induced a greater 5 HT release than did L-deprenyl, but was less effective than L-deprenyl in releasing DA. On the contrary, lazabemide was almost completely inactive on either 5 HT and DA release [2]. a clear inhibition of DOPAC formation was observed with Ro 41-1049 (250 nM), while 250 nM lazabemide was found not to increase the accumulation of newly-formed DA in those tubular epithelial cells loaded with 50 microM L-DOPA [3].in vivo: The ischemia reperfusion-induced hydroxyl radical generation was attenuated by 3 mg/kg of clorgyline and lazabemide. Furthermore, mice pretreated with these MAO inhibitors showed decreased DOPAC levels in comparison with those of their respective vehicle-treated control groups; recovery of the reduced DOPAC level was also delayed [4].

  • CAS Number: 103878-84-8
  • MF: C8H10ClN3O
  • MW: 199.637
  • Catalog: Monoamine Oxidase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 397.4±37.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.2±26.5 °C

BW 373U86

BW373U86 (SNC86) is a δ-opioid receptor agonist with an IC50 of 1.49 nM. BW373U86 shows antidepressant-like effects[1].

  • CAS Number: 155836-50-3
  • MF: C27H37N3O2
  • MW: 435.60
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Palonosetron-d3 hydrochloride

Palonosetron-d3 hydrochloride is the deuterium labeled Palonosetron hydrochloride. Palonosetron hydrochloride is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV)[1][2].

  • CAS Number: 1246816-81-8
  • MF: C19H22D3ClN2O
  • MW: 335.89
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY 334370

LY334370 is a selective 5-HT1F receptor agonist with a Ki of 1.6 nM.

  • CAS Number: 182563-08-2
  • MF: C21H22FN3O
  • MW: 351.42
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 504.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 258.7ºC

Dasotraline (hydrochloride)

Dasotraline hydrochloride (SEP-225289 hydrochloride) is a triple reuptake inhibitor that blocks dopamine, norepinephrine, and serotonin transporters with IC50 values of 4, 6, and 11 nM, respectively.

  • CAS Number: 675126-08-6
  • MF: C16H16Cl3N
  • MW: 328.664
  • Catalog: Dopamine Transporter
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BIBN-99

BIBN-99 is a selective, BBB-penetrable and competitive muscarinic M2 receptor antagonist. BIBN-99 improves cognitive performancein rats with traumatic brain injury[1][2].

  • CAS Number: 145301-48-0
  • MF: C31H42ClN5O3
  • MW: 568.15000
  • Catalog: mAChR
  • Density: 1.172g/cm3
  • Boiling Point: 709.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 383.1ºC

SL-651,498

SL651498 is a full agonist of α2 and α3 GABAA receptors, and a partial agonist of α1 and α5 GABAA receptors. SL651498 shows anxiolytic and anticonvulsant activities[1].

  • CAS Number: 205881-86-3
  • MF: C23H20FN3O2
  • MW: 389.42200
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

8-Hydroxy-DPAT hydrobromide

8-Hydroxy-DPAT hydrobromide (8-OH-DPAT hydrobromide) is a potent and selective 5-HT1A agonist with a pIC50 of 8.19. 8-Hydroxy-DPAT hydrobromide has selectivity of almost 1000 fold for a subtype of the 5-HT1 binding site[1].

  • CAS Number: 76135-31-4
  • MF: C16H26BrNO
  • MW: 328.28800
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rupatadine

Rupatadine (UR-12592) is a potent dual PAF/H1 antagonist with Ki of 0.55/0.1 uM(rabbit platelet membranes/guinea pig cerebellum membranes).IC50 value:Target: PAF/H1 antagonistin vitro: Rupatadine competitively inhibited histamine-induced guinea pig ileum contraction (pA2 = 9.29 +/- 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 +/- 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or arachidonic acid-induced platelet aggregation [1]. The IC50 for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7+/-0.4 microM, 3.2+/-0.7 microM and 1.5+/-0.4 microM, respectively whereas for loratadine the IC50 was 2.1+/-0.9 microM, 4.0+/-1.3 M and 1.7+/-0.5 microM. SR-27417A exhibited no inhibitory effect [2].in vivo: Rupatadine blocked histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 micrograms/kg i.v.). Moreover, it potently inhibited PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.) [1]. rupatadine treatment improved the declined lung function and significantly decreased animal death. Moreover, rupatadine was able not only to attenuate silica-induced silicosis but also to produce a superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist loratadine, or PAF antagonist CV-3988 [3].

  • CAS Number: 158876-82-5
  • MF: C26H26ClN3
  • MW: 415.958
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 586.4±50.0 °C at 760 mmHg
  • Melting Point: 58-61ºC
  • Flash Point: 308.4±30.1 °C

Zicronapine

Zicronapine is an antipsychotic medication with a strong pro-cognitive effect in animal models and the potential to treat a number of neurological and psychiatric diseases. Zicronapine has potent antagonistic effects at dopamine D1/D2, and serotonin 5-HT2A receptors.

  • CAS Number: 170381-16-5
  • MF: C22H27ClN2
  • MW: 354.91600
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-Cinchonaminone

(+)-Cinchonaminone shows monoamine oxidase (MAO) inhibitory activity.

  • CAS Number: 60305-15-9
  • MF: C19H24N2O2
  • MW: 312.41
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydrexidine

Dihydrexidine (DAR-100) is a high potent, selective and full efficacy D1 dopamine receptor agonist with an IC50 of 10 nM, and displays some affinity for the D2 receptor. Dihydrexidine (DAR-100) exhibits potent antiparkinsonian activity[1][2][3].

  • CAS Number: 123039-93-0
  • MF: C17H17NO2
  • MW: 303.78300
  • Catalog: Dopamine Receptor
  • Density: 1.267g/cm3
  • Boiling Point: 488.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 190.5ºC

(+)-PHENSERINE

(+)-Phenserine is a novel selective cholinesterase noncompetitive inhibitor with an IC50 of 45.3 μM.

  • CAS Number: 116839-68-0
  • MF: C20H23N3O2
  • MW: 337.41600
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GLYX 13 TFA

Rapastinel (GLYX-13) is an N-methyl-D-aspartate receptor (NMDAR) modulator that has characteristics of a glycine site partial agonist. Target: NMDARapastinel is a robust cognitive enhancer and facilitates hippocampal long-term potentiation (LTP) of synaptic transmission in slices.

  • CAS Number: 117928-94-6
  • MF: C18H31N5O6
  • MW: 413.46900
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB 221284

SB 221284 is a selective 5-HT2C/2B receptor antagonist with pKi values are 6.4, 7.9 and 8.6 for 5-HT2A, 5-HT2B and 5-HT2C receptors, respectively. SB 221284 can be used for the research of neurological disease[1].

  • CAS Number: 196965-14-7
  • MF: C16H14F3N3OS
  • MW: 353.36200
  • Catalog: 5-HT Receptor
  • Density: 1.43g/cm3
  • Boiling Point: 536.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.1ºC

Amyloid β-Protein (10-20)

Amyloid β-Protein (10-20) is a fragment of Amyloid-β peptide, maybe used in the research of neurological disease.

  • CAS Number: 152286-31-2
  • MF: C71H99N17O16
  • MW: 1446.65000
  • Catalog: Peptides
  • Density: 1.302 g/cm3
  • Boiling Point: 1832.406ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 1062.001ºC

5-HT2A receptor agonist-1

5-HT2A receptor agonist-1 is a 5-HT2A receptor agonist with the EC50 of 5.54 nM. 5-HT2A receptor agonist-1 can be used for the research of mood disorders[1].

  • CAS Number: 2698331-34-7
  • MF: C15H22ClFN2
  • MW: 284.80
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML138

ML138, a κ opioid receptor agonist, is a MLPCN probe[1].

  • CAS Number: 1355243-24-1
  • MF: C19H14Cl2N4OS
  • MW: 417.312
  • Catalog: Opioid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 625.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 331.8±34.3 °C

L 760735

L-760735 is a high affinity, selective and orally active NK1 receptor antagonist with an IC50 of 0.19 nM for human NK1 receptors. L-760735 exhibits anxiolytic and antidepressant-like effects[1].

  • CAS Number: 188923-01-5
  • MF: C26H29ClF7N5O2
  • MW: 611.98
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-APPA(CGP 27492)(mM/ml)

3-Aminopropylphosphinic acid (3-APPA), a phosphonic analog of GABA, is a GABAB receptor agonist[1].

  • CAS Number: 103680-47-3
  • MF: C3H10NO2P
  • MW: 123.09
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dual FAAH/sEH-IN-1

Dual FAAH/sEH-IN-1 (compound 3) is a high affinity dual sEH (soluble epoxide hydrolase) and FAAH (fatty acid amide hydrolase) inhibitor, with IC50 values of 9.6 and 7 nM, respectively. Dual FAAH/sEH-IN-1 shows antinociception against the inflammatory phase[1].

  • CAS Number: 2756099-59-7
  • MF: C25H22ClN3O3S2
  • MW: 512.04
  • Catalog: FAAH
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aloeresin D

Aloeresin D is a chromone glycoside isolated from Aloe vera, inhibits β-Secretase (BACE1) activity, with an IC50 of 39 μM[1].

  • CAS Number: 105317-67-7
  • MF: C29H32O11
  • MW: 556.558
  • Catalog: Beta-secretase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 796.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 261.7±26.4 °C

Pirimiphos-methyl-d6

Pirimiphos-methyl-d6 is the deuterium labeled Pirimiphos-methyl. Pirimiphos-methyl is a rapid-acting organophosphorus insecticide and acaricide, causing inhibition of AChE in target organisms. Pirimiphos-methyl is often used for prevention and control of beetles, snout beetles, moths and Ephestia cautella during storage of agricultural grains[1][2][3].

  • CAS Number: 1793055-06-7
  • MF: C11H14D6N3O3PS
  • MW: 311.371
  • Catalog: AChE
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 386.5±52.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 187.6±30.7 °C

Safinamide

Safinamide (EMD 1195686; FCE 26743) selectively and reversibly inhibits MAO-B with IC50 of 98 nM, exhibits 5918-fold selectivity against MAO-A.IC50 value: 98 nM [1]Target: MAO-BSafinamide (EMD 1195686; FCE 26743; ) is a highly selective and reversible monoamine oxidase type B (MAO-B) inhibitor that increases neostriatal dopamine concentration. In addition, Safinamide (EMD 1195686; FCE 26743; ) is voltage-dependent sodium and calcium channel blocker. Safinamide (EMD 1195686; FCE 26743; ) appears to bind to the batrachotoxin-sensitive site 2 of the voltage-sensitive sodium channels. Safinamide blocks N and L-type calcium channels and inhibits glutamate and aspartate release from synaptic terminals.

  • CAS Number: 133865-89-1
  • MF: C17H19FN2O2
  • MW: 302.343
  • Catalog: Monoamine Oxidase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 476.7±40.0 °C at 760 mmHg
  • Melting Point: 208-212°
  • Flash Point: 242.1±27.3 °C

A 484954

A-484954 is a highly selective eukaryotic elongationfactor-2 (eEF2) inhibitor, with an IC50 of 280 nM.

  • CAS Number: 142557-61-7
  • MF: C13H15N5O3
  • MW: 289.29000
  • Catalog: CaMK
  • Density: 1.522±0.06 g/cm3 (20 ºC 760 Torr)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AChE/BChE-IN-4

AChE/BChE-IN-4 (BMC-3) is a dual AChE and BChE inhibitor with IC50 values of 792 nM and 2.2 nM against human AChE (hAChE) and human BChE (hBChE), respectively. AChE/BChE-IN-4 can cross the BBB[1].

  • CAS Number: 2294963-47-4
  • MF: C17H26N2O3
  • MW: 306.40
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

nAChR modulator-2

nAChR modulator-2, a insecticide, is a insect nAChR orthosteric modulator[1].

  • CAS Number: 1700657-87-9
  • MF: C12H8ClN3O2
  • MW: 261.66
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A