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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5-HT3-In-1

5-HT3-In-1 is extracted from patent EP0748807A1, compound example 8. It shows 5-HT3 inhibition activity.

  • CAS Number: 186348-68-5
  • MF: C16H21ClN4O3
  • MW: 352.82
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

B-HT 920

B-HT 920(Talipexole 2Hcl) is a dopamine D2 receptor agonist, α2-adrenoceptor agonist and 5-HT3 receptor antagonist, which displays antiParkinsonian activity.IC50 Value: 25 nM(Adrenergic receptor α-2, rat)Target: Adrenergic Receptor; 5-HT Receptor; Dopamine Receptorin vitro: N/Ain vivo: Intravenous injection of 30 micrograms/kg of B-HT 920 into cats lead initially to an increase in blood pressure and then to a long-lasting decrease in blood pressure and heart rate. Vagally mediated reflex bradycardia elicited by angiotensin injection in beta-adrenoceptor-blocked dogs was facilitated by intracisternal injection of 10 micrograms/kg B-HT 920.

  • CAS Number: 36085-73-1
  • MF: C10H17Cl2N3S
  • MW: 282.233
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 364.6ºC at 760mmHg
  • Melting Point: 245ºC dec.
  • Flash Point: 174.3ºC

Olcegepant

Olcegepant is a potent and selective non-peptide antagonist of the calcitonin gene-related peptide 1 (CGRP1) receptor with IC50 of 0.03 nM and Ki of 14.4 pM for human CGRP.

  • CAS Number: 204697-65-4
  • MF: C38H47Br2N9O5
  • MW: 869.64500
  • Catalog: CGRP Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Felbamate-d4

Felbamate-d4 (W-554-d4) is the deuterium labeled Felbamate. Felbamate (W-554) is a potent nonsedative anticonvulsant whose clinical effect may be related to the inhibition of N-methyl-D-aspartate (NMDA).

  • CAS Number: 106817-52-1
  • MF: C11H10D4N2O4
  • MW: 242.26500
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dopamine D2 receptor antagonist-1

Dopamine D2 receptor antagonist-1 is a negative allosteric modulator (NAM) of the dopamine D2 receptor (D2R) with sub-mM affinity[1].

  • CAS Number: 1055411-77-2
  • MF: C14H17N3S
  • MW: 259.37
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[MePhe8,Sar9] Substance P

[MePhe8,Sar9] Substance P ([MePhe8-MeGly9] Substance P) is an analog of Substance P (Substance P (HY-P0201)).Substance P is a neuropeptide, acting as a neurotransmitter and as a neuromodulator in the CNS[1].

  • CAS Number: 77128-76-8
  • MF: C65H102N18O13S
  • MW: 1375.68
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cl-HIBO

Cl-HIBO is a highly subtype-selective GluR1/2 agonist (EC50=4.7 and 1.7 μM, respectively). Cl-HIBO is a potent AMPA receptor agonist (IC50=0.22 μM). Cl-HIBO has desensitizing properties[1].

  • CAS Number: 909400-43-7
  • MF: C6H7ClN2O4
  • MW: 206.58400
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-Mirtazapine-13C-d3

(S)-Mirtazapine ((S)-Org3770) is a S(+)-enantiomer of Mirtazapine with pronociceptive properties in an animal model of acute thermal nociception. (S)-Mirtazapine is a stereoselective 5-HT2 receptor antagonist. (S)-Mirtazapine is metabolized by CYP2D6 and CYP1A2[1].

  • CAS Number: 61337-87-9
  • MF: C17H19N3
  • MW: 265.353
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 432.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 215.3±28.7 °C

Piribedil D8

Piribedil D8 is the deuterium labeled Piribedil, which is an antiparkinsonian agent.

  • CAS Number: 1398044-45-5
  • MF: C16H10D8N4O2
  • MW: 306.389
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 469.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 237.7±31.5 °C

Flavoxate hydrochloride

Flavoxate Hydrochloride(DW-61 Hydrochloride) is a muscarinic AChR antagonist used in various urinary syndromes and as an antispasmodic.Target: mAChRFlavoxate displaces [3H]nitrendipine on the Ca2+ channels binding sites with IC50 of 254 μM [1]. Flavoxate (>10 μM) suppresses carbachol-induced contractions in isolated rat detrusor strips with pD value of 4.55. Flavoxate (>10 μM) suppresses Ca2+-induced contractions in isolated rat detrusor strips with pIC50 value of 4.92 [2]. Flavoxate (0.01 μM ?10 μM) inhibits CAMP formation in a concentration-dependent manner in membranes from the rat striatum and cerebral cortex, an action which is completely abolished by pretreating the membranes with pertussis toxin (PTX) [3].Flavoxate (10mg/kg) suppresses both the an initial, rapidly rising phasic contraction (phase 1) and the tonic contraction (phase 2) contractions to the same extent in rats. Flavoxate (10mg/kg) abolishes the bladder contractions without causing any change in the amplitude of the contractions in rats. Flavoxate (3 mg/kg) abolishes the efferent neural activity and the associated bladder contractions for about 10 minutes without changing the baseline vesical pressure in rats. ICV-injected (50 to 200 μg/rat) or IT-injected (100 to 200 μg/rat) Flavoxate abolishes rhythmic bladder contractions during and after injection for five to 15 minutes in a dose-dependent manner in rats [2]. Flavoxate (3 mg/kg, i.v.) abolishes rhythmic bladder contractions and the maximal intervals of voiding contractions is 7.20 min [3].

  • CAS Number: 3717-88-2
  • MF: C24H26ClNO4
  • MW: 427.921
  • Catalog: mAChR
  • Density: 1.203g/cm3
  • Boiling Point: 564.1ºC at 760 mmHg
  • Melting Point: 232-234°C
  • Flash Point: 294.9ºC

N-[(1S,5R)-7,9-dimethyl-7,9-diazabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide dihydrochloride

Indisetron dihydrochloride is a 5-HT3 receptor antagonist with anti-emetic activity.

  • CAS Number: 160472-97-9
  • MF: C17H25Cl2N5O
  • MW: 386.32
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 574.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 301.2ºC

Eltoprazine

Eltoprazine(DU28853) is a serenic or antiaggressive agent which as an agonist at the 5-HT1A and 5-HT1B receptors and as an antagonist at the 5-HT2C receptor.IC50 value:Target: 5-HT1A/1B agonist; 5-HT2C antagonistin vitro: The binding of [3H]eltoprazine to whole tissue sections was saturable and revealed an apparent dissociation constant (Kd) of 11 nM. Specific [3H]eltoprazine binding was completely displaced by 5-HT; conversely, unlabelled eltoprazine reduced [3H]5-HT binding to the levels of non-specific binding [1]. Eltoprazine evoked membrane changes that were similar to but much weaker than those induced by 5HT. Both the 5HT- and eltoprazine-evoked membrane hyperpolarizations were largely suppressed in the presence of spiperone [2].in vivo: eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l-dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models [3]. Rats were chronically treated with mianserin (10 mg/kg i.p.) or eltoprazine (1 mg/kg i.p.) and were tested in the elevated plus-maze test for anxiety. Mianserin and eltoprazine displayed opposite effects in the elevated plus-maze: mianserin induced anxiolytic-like effects, while eltoprazine showed anxiogenic-like ones [4].

  • CAS Number: 98224-03-4
  • MF: C12H16N2O2
  • MW: 220.26800
  • Catalog: 5-HT Receptor
  • Density: 1.18g/cm3
  • Boiling Point: 384.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 186.2ºC

Rat CGRP-(8-37)

Rat CGRP-(8-37) (VTHRLAGLLSRSGGVVKDNFVPTNVGSEAF) is a highly selective CGRP receptor antagonist.

  • CAS Number: 129121-73-9
  • MF: C138H224N42O41
  • MW: 3127.51000
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY310762

LY310762 is a 5-HT1D receptor antagonist with Ki of 249 nM, having a weaker affinity for 5-HT1B receptor.IC50 value: 249 nM (Ki) [1]Target: 5-HT1D in vitro: LY310762 has a higher affinity for the guinea pig 5-HT1D receptor than for the 5-HT1B receptor. LY310762 potentiates the potassium-induced [3H]5-HT outflow from guinea pig cortical slices with an EC50 of 30 nM. The maximum potentiation of the potassium-induced outflow which is obtained with LY310762 is about 40% [1]. LY310762 blocks the decreased EPSC amplitude induced by Sumatriptan [2]. in vivo: Systemic administration of LY310762 (10 mg/kg i.p.) produces a further significant enhancement in the 5-HT response to fluoxetine (20 mg/kg i.p.) when compared to animals receiving a control vehicle injection. In fluoxetine treated animals, levels of 5-HT increases from 312±43% to a maximum of 683% after LY310762. In control animals, levels of 5-HT remains unchanged (250%). LY310762 administered alone also significantly increases basal levels of 5-HT above vehicle controls, reaching a maximum of 258% compared to the pre-injection control [1].

  • CAS Number: 192927-92-7
  • MF: C24H28ClFN2O2
  • MW: 430.94300
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Imipramine hydrochloride

Imipramine hydrochloride inhibits serotonin transporter with an IC50 value of 32 nM in vitro.

  • CAS Number: 113-52-0
  • MF: C19H25ClN2
  • MW: 316.868
  • Catalog: Serotonin Transporter
  • Density: 1.041g/cm3
  • Boiling Point: 403.1ºC at 760mmHg
  • Melting Point: 168-1700C
  • Flash Point: 179.7ºC

Fluoroethylnormemantine

Fluoroethylnormemantine, a derivative of Memantine, is an antagonist of the N-methyl-D-aspartate (NMDA) receptor. [18F]-Fluoroethylnormemantine can be used as a positron emission tomography (PET) tracer. Fluoroethylnormemantine exhibits anti-amnesic, neuroprotective, antidepressant-like and fear-attenuating effects[1][2][3].

  • CAS Number: 1639210-26-6
  • MF: C12H20FN
  • MW: 197.29
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP-101606 mesylate

Traxoprodil mesylate (CP101,606) is a potent and selective NMDA antagonist and protect hippocampal neurons with an IC50 of 10 nM.

  • CAS Number: 188591-67-5
  • MF: C21H29NO6S
  • MW: 423.52
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Org 25543 hydrochloride

Org 25543 hydrochloride is a selective and irreversible GlyT2 inhibitor (IC50: 16 nM). Org 25543 hydrochloride has analgesia effect. Org 25543 hydrochloride ameliorates mechanical allodynia after partial sciatic nerve ligation injury in mice[1][2][3].

  • CAS Number: 495076-64-7
  • MF: C24H33ClN2O4
  • MW: 448.98
  • Catalog: GlyT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ST1936 oxalate

ST1936 oxalate is a selective, nanomolar affinity 5-HT6 receptor agonist with Ki values of 13 nM, 168 nM and 245 nM for human 5-HT6, 5-HT7 and 5-HT2B receptors, respectively. ST1936 oxalate also shows moderate affinity (Ki of 300 nM) for human α2 adrenergic receptor[1].

  • CAS Number: 1782228-83-4
  • MF: C15H19ClN2O4
  • MW: 326.78
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[D-Trp7,9,10]-Substance P TFA

[D-Trp7,9,10]-Substance P is the substance P analog that inhibits activation of Gq/11 by M1 muscarinic ACh receptors. [D-Trp7,9,10]-Substance P does not inhibit Gi/o activation by M2 ACh receptors.

  • CAS Number: 89430-38-6
  • MF: C79H105N21O13S
  • MW: 1588.88000
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RLH-033

RLH-033 is a potent and selective ligand for the sigma 1 recognition site. RLH-033 has high affinity for sigma 1 sites labeled by [3H](+)-pentazocine with a Ki of 50 pM[1].

  • CAS Number: 157097-10-4
  • MF: C25H31ClN2O4
  • MW: 458.97800
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 571.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 299.4ºC

Neurokinin antagonist 1

Neurokinin antagonist 1 is a Neurokinin antagonist extracted from patent WO1998045262A1.

  • CAS Number: 214487-45-3
  • MF: C38H40N4O3
  • MW: 600.75
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GR103545

GR103545 is a potent and selective agonist of the κ-opioid receptor (κ-OR). 11GR103545 is a radiotracer for imaging κ-OR in vivo[1][2].

  • CAS Number: 126766-43-6
  • MF: C23H29Cl2N3O7
  • MW: 530.40
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Aminobutanoic acid

γ-Aminobutyric acid (4-Aminobutyric acid) is a major inhibitory neurotransmitter in the adult mammalian brain[1][2], binding to the ionotropic GABA receptors (GABAA receptors) and metabotropic receptors (GABAB receptors)[2].

  • CAS Number: 56-12-2
  • MF: C4H9NO2
  • MW: 103.120
  • Catalog: Fungal
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 248.0±23.0 °C at 760 mmHg
  • Melting Point: 195-204ºC
  • Flash Point: 103.8±22.6 °C

Naftidrofuryl (oxalate)

Naftidrofuryl is a drug used in the management of peripheral and cerebral vascular disorders as a vasodilator, enhance cellular oxidative capacity, and may also be a 5-HT2 receptor antagonist.Target: 5-HT2 receptorNaftidrofuryl may be effective for relieving the pain of muscle cramps.[1]Naftidrofuryl oxalate is the only vasoactive drug for peripheral arterial disease (PAD) which is likely to be cost-effective.[2]Naftidrofuryl oxalate is ranked first for both maximum walking distance (MWD) and pain-free walking distance (PFWD) (probability of 0·947 and 0·987, respectively, of being the best treatment) followed by cilostazol and pentoxifylline. Naftidrofuryl oxalate is effective treatments for claudication, Naftidrofuryl oxalate is likely to be the most effective, with minimal serious adverse events.[3]

  • CAS Number: 3200-06-4
  • MF: C26H35NO7
  • MW: 473.55900
  • Catalog: 5-HT Receptor
  • Density: 1.2205 (rough estimate)
  • Boiling Point: 574°C (rough estimate)
  • Melting Point: 110-111°
  • Flash Point: N/A

[Sar9] Substance P

[Sar9] Substance P is a potent and selective neurokinin (NK)-1 receptor agonist[1].

  • CAS Number: 77128-75-7
  • MF: C64H100N18O13S
  • MW: 1361.66
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pimavanserin

Pimavanserin is a selective inverse agonist of the 5-HT2A receptor with pIC50 and pKd of 8.73 and 9.3, respectively.

  • CAS Number: 706779-91-1
  • MF: C25H34FN3O2
  • MW: 427.555
  • Catalog: 5-HT Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 604.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 319.2±31.5 °C

Bupivacaine Hydrochloride

Bupivacaine hydrochloride monohydrate is a NMDA receptor inhibitor. Bupivacaine hydrochloride monohydrate can block sodium, L-calcium, and potassium channels. Bupivacaine hydrochloride monohydrate potently blocks SCN5A channels with the IC50 of 69.5 μM. Bupivacaine hydrochloride monohydrate can be used for the research of chronic pain[1][2][3].

  • CAS Number: 73360-54-0
  • MF: C18H31ClN2O2
  • MW: 342.90
  • Catalog: Calcium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 255-259℃
  • Flash Point: N/A

β2AR/M-receptor agonist-1

β2AR/M-receptor agonist-1 (example 131) is a muscarinic antagonist and β2 adrenoceptor agonist (MABA). β2AR/M-receptor agonist-1 shows potency to β2 adrenoceptor with an EC50 value of 9.2 nM. β2AR/M-receptor agonist-1 also has potency to muscarinic receptor with a Ki value of 30.2 nM. β2AR/M-receptor agonist-1 shows MABA potency with an EC50 value of 4.0 nM[1].

  • CAS Number: 2230520-62-2
  • MF: C43H56BrN3O7
  • MW: 806.82
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NGP555

NGP555 is a γ-secretase modulator.

  • CAS Number: 1304630-27-0
  • MF: C23H23FN4S
  • MW: 406.519
  • Catalog: γ-secretase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 574.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 301.5±32.9 °C