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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1-(4-Aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride

GYKI 52466 hydrochloride is an orally active, highly selective and noncompetitive AMPA/kainate receptor antagonist with the IC50 values of 7.5 and 11μM, respectively. GYKI 52466 hydrochloride has good blood brain barrier permeability and anticonvulsant effect. GYKI 52466 hydrochloride can be used in Parkinson's disease research[1][2].

  • CAS Number: 192065-56-8
  • MF: C17H16ClN3O2
  • MW: 329.78
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

QWF

QWF Peptide (Compound 4a) is a substance P antagonist with an IC50 of 0.09 μM. QWF Peptide antagonizes the SP-induced contraction of isolated guinea pig trachea strips with an IC50 of 4.7 μM[1].

  • CAS Number: 126088-82-2
  • MF: C38H43N5O8
  • MW: 697.78
  • Catalog: Neurokinin Receptor
  • Density: 1.26g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-986188

BMS-986188 is a selective positive allosteric modulator of δ-opioid receptor with an EC50 of 0.05 μM[1].

  • CAS Number: 1776115-10-6
  • MF: C30H31BrO4
  • MW: 535.47
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

eucatropine

Eucatropine is a potent muscarinic acetylcholine receptor (mAChR) inhibitor with an IC50 value of 0.583 μM. Eucatropine is an anticholinergic agent[1].

  • CAS Number: 100-91-4
  • MF: C17H25NO3
  • MW: 291.38500
  • Catalog: mAChR
  • Density: 1.11g/cm3
  • Boiling Point: 388.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 188.8ºC

Trihexylphenedyl

Trihexyphenidyl is a potent and selective M1 muscarinic receptor antagonist. Trihexyphenidyl shows anticholinergic activity, and can be used for Parkinson syndrome or dystonia research[1][2].

  • CAS Number: 144-11-6
  • MF: C20H31NO
  • MW: 301.46600
  • Catalog: mAChR
  • Density: 1.04g/cm3
  • Boiling Point: 447.9ºC at 760 mmHg
  • Melting Point: 258.5ºC
  • Flash Point: 211ºC

Propantheline

Propantheline is an orally active mAChR antagonist. Propantheline can be used in the research of smooth muscle dysfunction, excessive sweating, cramps or spasms of the stomach, intestines or bladder, and involuntary urination[1][2][3].

  • CAS Number: 298-50-0
  • MF: C16H26N2O3
  • MW: 294.38900
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY 293284

LY 293284 is a potent and selective 5-HT1A receptor agonist. LY 293284 results in a significant drop in core temperature and consumes more food in cholestasis rat induced by bile duct resection[1][2].

  • CAS Number: 141318-62-9
  • MF: C19H26N2O
  • MW: 298.42
  • Catalog: 5-HT Receptor
  • Density: 1.11g/cm3
  • Boiling Point: 478.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 243ºC

UB 165 fumarate

UB-165 is a nAChR agonist, being a full agonist of the α3β2 isoform and a partial agonist of the α4β2* isoform, with a Ki value of 0.27 nM for [3H]-nicotine binding in rat brain[1].

  • CAS Number: 200432-86-6
  • MF: C17H19ClN2O4
  • MW: 350.79700
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: 597.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 315.1ºC

(S)-Cipepofol

(S)-Cipepofol is the inactive isomer of Cipepofol (HY-116152).Cipepofol (HSK3486) is a sleep-promoting active molecule and a gamma-aminobutyric acid (GABA) receptor enhancer[1].

  • CAS Number: 1637741-59-3
  • MF: C14H20O
  • MW: 204.31
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-0657

Rislenemdaz (CERC-301) is an orally bioavailable and selective N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B) antagonist with Ki and IC 50 of 8.1 nM and 3.6 nM, respectively.

  • CAS Number: 808732-98-1
  • MF: C19H23FN4O2
  • MW: 358.410
  • Catalog: iGluR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 527.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.7±32.9 °C

Calcitonin Gene Related Peptide Fragment 8-37 human

HCGRP-(8-37) is a human calcitonin gene-related peptide (hCGRP) fragment and also an antagonist of CGRP receptor. Sequence: Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser-Arg-Ser-Gly-Gly-Val-Val-Lys-Asn-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe.

  • CAS Number: 119911-68-1
  • MF: C139H230N44O38
  • MW: 3125.59000
  • Catalog: Peptides
  • Density: 1.46±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SKF 83822 hydrobromide

SKF83822 hydrobromide is a potent dopamine D1 receptor agonist. SKF83822 hydrobromide activates Gs/olf/adenylyl cyclase (AC)-coupled D1 receptors, but not phospholipase C (PLC)-coupled D1-like receptors[1].

  • CAS Number: 74115-10-9
  • MF: C20H23BrClNO2
  • MW: 424.76
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY 404187

LY-404187 is a potent, selective and centrally active positive allosteric modulator of AMPA receptors, with the EC50s of 5.65, 0.15, 1.44, 1.66 and 0.21 µM for GluR1i, GluR2i, GluR2o, GluR3i and GluR4i, respectively. LY-404187 has therapeutic potential in a number of psychiatric disorders and neurodegenerative diseases[1][2].

  • CAS Number: 211311-95-4
  • MF: C19H22N2O2S
  • MW: 348.503
  • Catalog: iGluR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 498.4±47.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 255.2±29.3 °C

Trazodone

Trazodone (AF-1161 free base) is a serotonin receptor antagonist and reuptake inhibitor. Trazodone can be used for the research of major depressive disorder. Trazodone also has potential for sleep disorder research[1].

  • CAS Number: 19794-93-5
  • MF: C19H22ClN5O
  • MW: 371.86
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 528.5±60.0 °C at 760 mmHg
  • Melting Point: 86-87ºC
  • Flash Point: 273.4±32.9 °C

ZP 120C

ZP 120C is a potent and partial ORL1 receptor agonist. ZP 120C inhibits electrically induced contraction. ZP 120C can be used in the research of hyponatremia/hypokalemia[1][3].

  • CAS Number: 383123-18-0
  • MF: C85HN27O15
  • MW: 1781.20
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carprofen

Carprofen is a nonsteroid anti-inflammatory agent, acts as a multi-target FAAH/COX inhibitor, with IC50s of 3.9 μM, 22.3 μM and 78.6 μM for COX-2, COX-1 and FAAH, respectively.

  • CAS Number: 53716-49-7
  • MF: C15H12ClNO2
  • MW: 273.714
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 509.1±35.0 °C at 760 mmHg
  • Melting Point: 186-188ºC
  • Flash Point: 261.7±25.9 °C

BP 897

BP 897 is a potent and selective dopamine D3 receptor agonist, and a weak dopamine D2 receptor antagonist, with Kis of 0.92 nM and 61 nM for D3 and D2 receptors, and shows low affinities at D1 and D4 receptors (Kis, 3 and 0.3 µM, respectively).

  • CAS Number: 314776-92-6
  • MF: C26H32ClN3O2
  • MW: 454.004
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 654.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 349.6ºC

PNU-120596

PNU-120596 (NSC 216666 ) is a potent and selective positive allosteric α7 nAChR modulator with an EC50 of 0.2 μM.IC50 value: 0.2 uM (EC50) [1] Target: α7in vitro: PNU-120596 increases agonist (Ach)-evoked calcium flux mediated by an engineered variant of the human α7 nAChR. PNU-120596 increases agonists (choline and ACh)-evoked currents mediated by wild-type receptors and also demonstrates a pronounced prolongation of the evoked response in the continued presence of agonist in Xenopus oocytes. PNU-120596 increases the channel mean open time ofα7 nAChRs but has no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increases the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect is suppressed by TTX, suggesting that PNU-120596 modulates the function of α7 nAChRs located on the somatodendritic membrane of hippocampal interneurons [1]. Besides the positive modulation to α7 nAChR, PNU-120596 induces a profound retardation of the kinetics of desensitization, raising the potential of Ca2+-induced toxicity through excessive stimulation of α7 nAChR [2]. PNU-120596 causes changes in cysteine accessibility at the inner beta sheet, transition zone and agonist binding site while binding to α7 nAChR. Binding sites for PNU-120596 are not in the agonist-binding sites and PNU-120596 enhances agonist-evoked gating of nicotinic receptors by eliciting conformational effects that are similar but nonidentical to the gating conformations promoted by Ach [3].in vivo: Systemic administration of PNU-120596 (1 mg/kg) to rats improves the auditory gating deficit caused by amphetamine, a model proposed to reflect a circuit level disturbance associated with schizophrenia. [1] When administered prior to Carrageenan, 30 mg/kg PNU-1230596 significantly blunts mechanical hyperalgesia and weight bearing deficits for up to 4 hours. PNU-120596 attenuates the carrageenan-induced increase in levels of TNF-α and IL-6 within the hindpaw oedema, diclofenac only attenuated IL-6 levels. Established mechanical hyperalgesia induced by Carrageenan or CFA is also partially reversed by PNU-120596 [4].

  • CAS Number: 501925-31-1
  • MF: C13H14ClN3O4
  • MW: 311.721
  • Catalog: nAChR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 385.0±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 186.6±27.9 °C

ORL1 antagonist 1

ORL1 antagonist 1 is an opioid receptor-like 1 (ORL1) antagonist with an IC50 of 61 nM.

  • CAS Number: 1174985-59-1
  • MF: C20H22ClN5
  • MW: 367.88
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pericyazine-d4

Pericyazine-d4 (Propericiazine-d4) is the deuterium labeled Pericyazine. Pericyazine (Propericiazine) is a first-generation antipsychotic agent that is used as an adjunct to the short-term management of severe anxiety states and psychosis[1]. Pericyazine is a selective D2-dopamine receptor antagonist[2][3]. Pericyazine has adrenolytic, anticholinergic, and extrapyramidal effects[4].

  • CAS Number: 1329836-72-7
  • MF: C21H19D4N3OS
  • MW: 369.52
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

nAChR agonist CMPI hydrochloride

nAChR agonist CMPI hydrochloride is a potent and selective positive allosteric modulator (PAM) of nAChR containing a α4:α4 subunit interface. nAChR agonist CMPI hydrochloride enhances the response of (α4)3(β2)2 nAChR to ACh (10 µM) with an EC50 of 0.26 µM. nAChR agonist CMPI hydrochloride has potential for the research of nicotine dependence and many neuropsychiatric conditions associated with decreased brain cholinergic activity[1][2].

  • CAS Number: 2250025-94-4
  • MF: C18H20Cl2N4O
  • MW: 379.28
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rasagiline mesylate

Rasagiline Mesylate is a new MAO-B inhibitor for the treatment of idiopathic Parkinson's disease. Target: Monoamine Oxidase (MAO)-BRasagiline (N-propargyl-1-(R)-aminoindan) is a novel, highly potent irreversible monoamine oxidase (MAO)-B inhibitor, anti-Parkinsonian drug. Rasagiline is effective as monotherapy or adjunct to L-Dopa for patients with early and late Parkinson's disease (PD) [1]. Rasagiline inhibits MAO-B more potently than selegiline and has the advantage of once-daily dosing. In several large, randomized, placebo-controlled trials, rasagiline has demonstrated efficacy as monotherapy in early PD and as adjunctive therapy in advanced PD. In addition, rasagiline has been shown to have neuroprotective effects in in vitro and in vivo studies. The recently completed delayed-start ADAGIO (Attenuation of Disease Progression with Azilect Given Once-daily) trial suggests a potential disease-modifying effect for rasagiline 1 mg/day, though the clinical import of this finding has yet to be established [2]. Rasagiline has been found to be well tolerated and effective in the treatment of early PD and as adjunctive treatment in motor fluctuations. Whether rasagiline is associated with clinically significant neuroprotection (ie, disease modification) in PD is the subject of ongoing clinical trials [3].

  • CAS Number: 161735-79-1
  • MF: C13H17NO3S
  • MW: 267.344
  • Catalog: Autophagy
  • Density: 1.05 g/cm3
  • Boiling Point: 305.5ºC at 760 mmHg
  • Melting Point: 155-158°C
  • Flash Point: 146.8ºC

Edonerpic maleate

Edonerpic maleate is a novel neurotrophic agent which can inhibit amyloid-β peptides (Aβ).

  • CAS Number: 519187-97-4
  • MF: C20H25NO6S
  • MW: 407.481
  • Catalog: Amyloid-β
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6β-Naltrexol

6β-Naltrexol (6β-Hydroxynaltrexone), the primary metabolite of Naltrexone, is a peripherally selective opioid antagonist. 6β-Naltrexol selectively inhibits gastrointestinal opioid effects in human subjects and inhibits Morphine-induced slowing of gastrointestinal transit[1].

  • CAS Number: 49625-89-0
  • MF: C20H25NO4
  • MW: 343.42
  • Catalog: Opioid Receptor
  • Density: 1.48g/cm3
  • Boiling Point: 557.5ºC at 760mmHg
  • Melting Point: 90-96ºC
  • Flash Point: 291ºC

5-Nitro-α-oxo-N-(1R)-phenylethyl]-1H-indole-3-acetamide

Anxiolytic/nonsedative agent-1 (compound 2b) is a potent and selective GABAA agonist. Anxiolytic/nonsedative agent-1 shows appreciable affinity for the BzR in bovine brain membranes with Kis of 14, 121, 239 nM for α1β2γ2, α2β2γ2, α5β3γ2, respectively. Anxiolytic/nonsedative agent-1 shows α2 selective efficacy in vitro and anxioselective effects in vivo[1].

  • CAS Number: 355022-97-8
  • MF: C18H15N3O4
  • MW: 337.32900
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Syn-ake

Dipeptide diaminobutyroyl benzylamide diacetate, a Wagerlin-1-mimicking peptide, is a mAChR antagonist. Dipeptide diaminobutyroyl benzylamide diacetate can induce muscle relaxation[1].

  • CAS Number: 823202-99-9
  • MF: C23H37N5O7
  • MW: 495.57
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cebranopadol

Cebranopadol is an analgesic NOP and opioid receptor agonist with Kis/EC50s of 0.9 nM/13 nM, 0.7 nM/1.2 nM, 2.6 nM/17 nM, 18 nM/110 nM for human NOP, MOP, KOP and delta-opioid peptide (DOP) receptor, respectively.

  • CAS Number: 863513-91-1
  • MF: C24H27FN2O
  • MW: 378.482
  • Catalog: Opioid Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 547.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 284.9±30.1 °C

Octahydroaminoacridine succinate

Octahydroaminoacridine, a Tacrine analogue, is an acetylcholinesterse (AChE) and butyrylcholinesterase (BChE) inhibitor. Octahydroaminoacridine can be used for Alzheimer's disease (AD) research[1].

  • CAS Number: 13415-07-1
  • MF: C13H18N2
  • MW: 202.30
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CART (62-76) (human, rat) trifluoroacetate salt

CART(62-76)(human,rat) is a neuropeptide (62-76 residues of the CART peptide) with neurotransmitter-like effects. CART(62-76)(human,rat) can modulate the activity of striatal noradrenergic and corticostriatal and hypothalamic serotoninergic (5-HT) system in the rat brain[1].

  • CAS Number: 210978-19-1
  • MF: C64H99N17O23S3
  • MW: 1570.77000
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

β-Secretase Inhibitor IV

β-Secretase Inhibitor IV is a potent, cell-active BACE-1 inhibitor with IC50s of 15.6 and 16.3nM under BACE-1 concentrations of 2 nM and 100 pM, respectively.

  • CAS Number: 797035-11-1
  • MF: C31H38N4O5S
  • MW: 578.72
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A