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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ETHYLAMINE, 2-CYCLOHEXYL-N-METHYL-

N-2-Cyclohexylethyl-N-methylamine is an amine from A.ridigula Benth for a reduction of monoamine oxidase (MAO) activity[1].

  • CAS Number: 62141-38-2
  • MF: C9H19N
  • MW: 141.25400
  • Catalog: Monoamine Oxidase
  • Density: 0.834g/cm3
  • Boiling Point: 184.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 55.6ºC

mGAT3/4-IN-2

mGAT3/4-IN-2 (compound 27b) is a potent mGAT3/mGAT4 inhibitor, with pIC50 values of 5.44 and 5.25, respectively[1].

  • CAS Number: 2556833-68-0
  • MF: C26H32ClN3OS2
  • MW: 502.13
  • Catalog: GABA Receptor
  • Density: N/A
  • 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

Substance P (6-11)

Substance P (6-11) is the C-terminal hexapeptideamide of Substance P (Substance P (HY-P0201)). Substance P (6-11) binds to NK-1 tachykinin receptor. Substance P (6-11) shows depolarization of motoneurons and a hypotensive effect[1][2].

  • CAS Number: 51165-07-2
  • MF: C36H52N8O7S
  • MW: 740.91200
  • Catalog: Neurokinin Receptor
  • Density: 1.24g/cm3
  • Boiling Point: 1198.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 678.9ºC

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

Tryptoline

Tetrahydro-β-carboline (Tryptoline) is a metabolite of tryptamine, also is a competitive serotonin reuptake inhibitor with an Ki value of 6.1 µM[1].

  • CAS Number: 16502-01-5
  • MF: C11H12N2
  • MW: 172.226
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 351.6±32.0 °C at 760 mmHg
  • Melting Point: 206-208 °C(lit.)
  • Flash Point: 166.5±25.1 °C

Z2CN

β-Aminopropionitrile is a specific and irreversible lysyl oxidase (LOX) inhibitor. β-Aminopropionitrile targets the active site of LOX or LOXL isoenzymes[1][2].

  • CAS Number: 151-18-8
  • MF: C3H6N2
  • MW: 70.093
  • Catalog: Monoamine Oxidase
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 186.3±13.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 66.5±19.8 °C

Rivastigmine carbamate impurity

Rivastigmine carbamate impurity (3-Nitrophenyl ethyl(methyl)carbamate) is an impurity of Rivastigmine. Rivastigmine is an orally active and potent cholinesterase (ChE) inhibitor and inhibits butyrylcholinesterase (BChE) and acetylcholinesteras (AChE) with IC50s of 0.037 μM, 4.15 μM, respectively[1][2].

  • CAS Number: 1346242-31-6
  • MF: C10H12N2O4
  • MW: 224.21300
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ICI 199,441 hydrochloride

ICI 199441 is a potent and selective κ-opioid receptor agonist. ICI 199441 can improve heart resistance to ischemia/reperfusion[1].

  • CAS Number: 115199-84-3
  • MF: C21H25Cl3N2O
  • MW: 427.80
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: 532.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 276ºC

Rubrofusarin triglucoside

Rubrofusarin triglucoside is a glycoside compound isolated from Cassia obtusifolia Linn seeds. Rubrofusarin triglucoside inhibits human monoamine oxidase A (hMAO-A) with an IC50 of 85.5 μM[1].

  • CAS Number: 245724-07-6
  • MF:
  • MW:
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

L-Phenylalanine-d5

L-Phenylalanine-d5 is the deuterium labeled L-Phenylalanine. L-Phenylalanine ((S)-2-Amino-3-phenylpropionic acid) is an essential amino acid isolated from Escherichia coli. L-Phenylalanine is a α2δ subunit of voltage-dependent Ca+ channels antagonist with a Ki of 980 nM. L-phenylalanine is a competitive antagonist for the glycine- and glutamate-binding sites of N-methyl-D-aspartate receptors (NMDARs) (KB of 573 μM ) and non-NMDARs, respectively. L-Phenylalanine is widely used in the production of food flavors and pharmaceuticals[1][2][3][4].

  • CAS Number: 56253-90-8
  • MF: C9H6D5NO2
  • MW: 170.220
  • Catalog: Calcium Channel
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 307.5±30.0 °C at 760 mmHg
  • Melting Point: 270-275 °C (dec. )(lit.)
  • Flash Point: 139.8±24.6 °C

1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt

Dicloromezotiaz is a potent insecticide acting on nicotinic acetylcholine receptors (nAChRs). Dicloromezotiaz can be used to control a broad range of lepidoptera[1].

  • CAS Number: 1263629-39-5
  • MF: C19H12Cl3N3O2S
  • MW: 452.741
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PNU-282987 S enantiomer free base

PNU-282987 S enantiomer free base is the S-enantiomer of PNU-282987 free base. PNU-282987 is an α7 nicotinic acetylcholine receptor (α7 nAChR) agonist.

  • CAS Number: 737727-12-7
  • MF: C14H17ClN2O
  • MW: 264.751
  • Catalog: nAChR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 431.5±30.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 214.8±24.6 °C

(+)-Borneol

(+)-Borneol (d-Borneol) is a natural bicyclic monoterpene used for analgesia and anesthesia in traditional Chinese medicine; enhances GABA receptor activity with an EC50 of 248 μM.

  • CAS Number: 464-43-7
  • MF: C10H18O
  • MW: 154.249
  • Catalog: GABA Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 212.0±0.0 °C at 760 mmHg
  • Melting Point: 206-209ºC(lit.)
  • Flash Point: 80.7±10.9 °C

3-[2-[4-(3,4-dimethylphenyl)-1-piperazinyl]ethyl]-2,3-dihydro-1H-isoindol-1-onedihydrochloride

PD 168568 is a orally active and potent dopamine receptor D4 (DRD4) antagonist. PD 168568 contains an isoindolinone and is selective for the D4 receptor versus D2 and D3, with Ki values of 8.8, 1842, and 2682 nM, respectively. PD 168568 can be used for glioblastoma (GBM) research[1][2].

  • CAS Number: 210688-56-5
  • MF: C22H29Cl2N3O
  • MW: 422.39100
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SKF 81297 hydrobromide

SKF 81297 hydrobromide is a potent and selective dopamine D1 receptor agonist[1].

  • CAS Number: 67287-39-2
  • MF: C16H17BrClNO2
  • MW: 370.669
  • Catalog: Dopamine 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

D4R agonist-1

D4R agonist-1 (Compound 16f) is a D4R partial agonist (Ki: 2.2 nM). D4R agonist-1 is metabolically stable in rat and human liver microsomes. D4R agonist-1 can be used for research of neuropsychiatric disorders[1].

  • CAS Number: 2826198-44-9
  • MF: C19H22N4S
  • MW: 338.47
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Glycine-13C2,15N

Glycine-13C2,15N is the 13C- and 15N-labeled Glycine. Glycine is an inhibitory neurotransmitter in the CNS and also acts as a co-agonist along with glutamate, facilitating an excitatory potential at the glutaminergic N-methyl-D-aspartic acid (NMDA) receptors.

  • CAS Number: 211057-02-2
  • MF: 13C2H515NO2
  • MW: 78.045
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 240ºC (dec.)(lit.)
  • Flash Point: N/A

homatropine hydrochloride

Homatropine hydrochloride is an orally active anticholinergic agent that rapidly dilates pupils and has cycloplegic effects. Homatropine hydrochloride also has antitussive activity. Homatropine hydrochloride can be used in research on eye diseases and coughs[1].

  • CAS Number: 637-21-8
  • MF: C16H22ClNO3
  • MW: 311.80
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 403.3ºC at 760 mmHg
  • Melting Point: 226ºC
  • Flash Point: 197.7ºC

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

AA38-3

AA38-3 is a serine hydrolase (SH) inhibitor. AA38-3 can inhibit three SHs, ABHD6, ABHD11, and FAAH[1].

  • CAS Number: 65815-76-1
  • MF: C12H14N2O4
  • MW: 250.25
  • Catalog: FAAH
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 397.5±34.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.2±25.7 °C

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

Aniracetam

Aniracetam(Ro 13-5057) is a nootropics and neuroprotective drug, which is selectively modulates the AMPA receptor and nAChR.Target: AMPA; nAChRAniracetam is an ampakine and nootropic of the racetam chemical class purported to be considerably more potent than piracetam. It selectively modulates the AMPA receptor. It is lipid soluble and has possible cognition enhancing effects. It has been tested in animals extensively, Alzheimer's patients and temporarily-impaired healthy subjects. It has shown potential as an anxiolytic in three clinical animal models [1].Administration of aniracetam for 10 days (post-natal days (PND) 18-27), at a dose of 50 mg/kg reversed cognitive deficits in both rat genders, indicated by a significant increase in the number of avoidances and the number of 'good learners'. After the termination of the nootropic treatment, a significant increase in both amplitude and frequency of AMPA receptor-mediated mEPSCs in hippocampal CA-1 pyramidal cells was observed [2].Clinical indications: Cognitive disorder; StrokeFDA Approved Date: Toxicity: insomnia; headaches; nausea or rash.

  • CAS Number: 72432-10-1
  • MF: C12H13NO3
  • MW: 219.236
  • Catalog: iGluR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 399.7±34.0 °C at 760 mmHg
  • Melting Point: −58 °C(lit.)
  • Flash Point: 195.5±25.7 °C

Rupatadine Fumarate

Rupatadine Fumarate (UR-12592 Fumarate) 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: 182349-12-8
  • MF: C30H30ClN3O4
  • MW: 532.030
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 586.4ºC at 760 mmHg
  • Melting Point: 58-61ºC
  • Flash Point: 308.4ºC