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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(-)-MDL 100907

(S)-Volinanserin is an isform of Volinanserin (HY-14940). Volinanserin is a potent and selective antagonist of 5-HT2 receptor, with a Ki of 0.36 nM, and shows 300-fold selectivity for 5-HT2 receptor over 5-HT1c, alpha-1 and DA D2 receptors. Volinanserin has antipsychotic activity.

  • CAS Number: 175673-57-1
  • MF: C22H28FNO3
  • MW: 373.46
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Edrophonium chloride

Edrophonium chloride is a readily reversible acetylcholinesterase inhibitor; prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting the enzyme acetylcholinesterase, mainly at the neuromuscular junction.

  • CAS Number: 116-38-1
  • MF: C10H16ClNO
  • MW: 201.693
  • Catalog: AChE
  • Density: 1.395 g/mL at 25 °C(lit.)
  • Boiling Point: 130 °C20 mm Hg(lit.)
  • Melting Point: 162-163°C
  • Flash Point: >230 °F

ABT 894

Sofiniclin (ABT 894) is an agonist of nicotinic acetylcholine receptor (nAChR), used as a potential non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD).

  • CAS Number: 799279-80-4
  • MF: C10H11Cl2N3
  • MW: 244.12000
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-745870 hydrochloride

L-745870 hydrochloride is a high-affinity, selective and orally active human dopamine D4 receptor antagonist with a Ki of 0.43 nM, and considerably weaker D2 (Ki of 960 nM) and D3 (Ki of 2300 nM) receptors affinity. L-745870 hydrochloride has excellent brain penetration[1][2][3].

  • CAS Number: 1173023-36-3
  • MF: C18H20Cl2N4
  • MW: 363.28
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(3S)-3-Isobutyl-2,5-piperazinedione

Cyclo(glycyl-L-leucyl) (Cyclo(leu-gly)), a neuropeptide, down-regulates dopamine (DA) receptors and attenuates dopaminergic supersensitivity. Cyclo(glycyl-L-leucyl) inhibits the development of Morphine induced pain relief as well as dopamine receptor supersensitivity in rats. Cyclo(glycyl-L-leucyl) has the potential for the prevention of tardive and/or L-DOPA (HY-N0304)-induced dyskinesias[1][2].

  • CAS Number: 5845-67-0
  • MF: C8H14N2O2
  • MW: 170.209
  • Catalog: Dopamine Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 442.9±38.0 °C at 760 mmHg
  • Melting Point: 255ºC
  • Flash Point: 207.4±26.9 °C

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

DWK-1339

DWK-1339 is an orally active and blood-brain-barrier-permeable Aβ-aggregation inhibitor, used in the research of Alzheimer's disease.

  • CAS Number: 1018946-38-7
  • MF: C20H22O4
  • MW: 326.38600
  • Catalog: Amyloid-β
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

sEH/AChE-IN-4

sEH/AChE-IN-4 (compound (+)-15) is a potent and BBB-penetrated dual inhibitor of sEH (soluble epoxide hydrolase) and AChE (acetylcholinesterase), with IC50 values of 3.1 nM (hsEH), 1660 nM (hAChE), 179 nM (hBChE, human butyrylcholinesterase), 14.5 nM (msEH), and 102 nM (mAChE), respectively[1].

  • CAS Number: 2490589-12-1
  • MF: C35H39ClF3N5O3
  • MW: 670.16
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DPNI-caged-GABA

DPNI-GABA is a nitroindoline cage compound that inhibits GABA(A) receptors and reduces GABA-evoked peak responses with an IC50 value of 0.5 mM[1].

  • CAS Number: 927866-58-8
  • MF: C15H23N3O12P2
  • MW: 499.30
  • Catalog: GABA Receptor
  • Density: 1.676±0.06 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: 900.8±75.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

Darifenacin

Darifenacin(UK88525) is a selective M3 muscarinic receptor antagonist with pKi of 8.9.IC50 value: 8.9 (pKi) [1]Target: M3 receptorin vitro: Darifenacin exerts non-parallel rightward displacement of the agonist curve and also significant depression of the maximum response (+)-cis-Dioxolane produced concentration-dependent contraction of the isolated bladder of rat [1]. Darifenacin produces a concentration dependent increase in R123 (P-gp probe) accumulation in MDCK cells. Darifenacin stimulates ATPase activity in P-gp membrane in a clear concentration dependent response manner with an estimated ED50 value of 1.6 μM. Darifenacin (100 nM) shows a significantly greater permeability for darifenacin in the basolateral to apical direction resulting in an efflux ratio in BBMEC monolayers of approximately 2.6 [2].in vivo: Darifenacin produces dose-dependent inhibition of amplitude of volume-induced bladder contractions(VIBCAMP), producing 35% inhibition at dose of 283.3 nmol/kg and maximal inhibition of approximately 50–55% [1]. Darifenacin (0.1 mg/kg i.v.) reduces bladder afferent activity in both Aδ and C fibers in female Sprague-Dawley rats, the decrease in afferent spikes in C fibers may be more pronounced than that in Aδ fibers [3].

  • CAS Number: 133099-04-4
  • MF: C28H30N2O2
  • MW: 426.550
  • Catalog: mAChR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 614.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 325.3±31.5 °C

Relenopride hydrochloride

Relenopride (YKP10811) hydrochloride is a specific and selective 5-HT4 receptor agonist (Ki=4.96 nM). Relenopride hydrochloride has 120-fold and 6-fold lower affinity, respectively, for 5-HT2A (Ki=600 nM) and 5-HT2B receptors (Ki=31 nM) than for 5-HT4. Relenopride hydrochloride increases gastrointestinal (GI) motility[1][2].

  • CAS Number: 1221416-42-7
  • MF: C24H31Cl2FN4O4
  • MW: 529.432
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

β-Endorphin (rat)

β-Endorphin (rat) is an endogenous opioid neuropeptide and peptide hormone. β-Endorphin (rat) has analgesic activity and also contributes to food intake in satiated rats. β-Endorphin (rat) can be used in the research of neurological diseases such as analgesia and drug addiction[1][2].

  • CAS Number: 309246-19-3
  • MF: C157H254N42O44S
  • MW: 3466.02
  • Catalog: Opioid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 2966.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 1748.0±34.3 °C

Lotilaner

Lotilaner is a parasiticide, acts as a potent non-competitive antagonist of insects GABACl receptors, with an IC50 of 23.84 nM for Drosophila melanogaster GABA receptor. No effect on a dog GABAA receptor[1].

  • CAS Number: 1369852-71-0
  • MF: C20H14Cl3F6N3O3S
  • MW: 596.76
  • Catalog: Parasite
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JDTic (dihydrochloride)

JDTic (dihydrochloride) is a potent antagonist of kappa-opioid receptors (KOR), blocking the κ-agonist U50, 488-induced antinociception.

  • CAS Number: 785835-79-2
  • MF: C28H41Cl2N3O3
  • MW: 538.54900
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Naxagolide

Naxagolide ((+)-PHNO; Dopazinol) is a potent dopamine D2 (Dopamine Receptor) agonist. Naxagolide has the potential for the research of parkinson's disease (PD)[1][2].

  • CAS Number: 88058-88-2
  • MF: C15H21NO2
  • MW: 247.333
  • Catalog: Dopamine Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 391.7±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 190.7±27.9 °C

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

Protriptyline hydrochloride

Protriptyline is a tricyclic antidepressant (TCA), specifically a secondary amine, for the treatment of depression and ADHD. Unique among the TCAs, protriptyline tends to be energizing instead of sedating, used for narcolepsy to achieve a wakefulness-promoting effect.

  • CAS Number: 1225-55-4
  • MF: C19H22ClN
  • MW: 299.838
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: 407.7ºC at 760 mmHg
  • Melting Point: 169-171°
  • Flash Point: 198.3ºC

FAAH-IN-8

FAAH-IN-8 (compound 11) is a competitive inhibitor of FAAH with an IC50 value of 6.7 nM and a Ki value of 5 nM. FAAH-IN-8 has high blood-brain permeability and a significant antioxidant profile with no neurotoxicity[1].

  • CAS Number: 2867633-84-7
  • MF: C18H14N4O
  • MW: 302.33
  • Catalog: FAAH
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-[2-[(1S,5S,7S)-7-(4-fluorophenyl)-3-azabicyclo[3.2.0]hept-3-yl]ethyl]-1H-quinazoline-2,4-dione

Belaperidone (LU-111995), a 5-HT2A receptor inhibitor, possesses antidopaminergic and antiserotonergic effects[1].

  • CAS Number: 208661-17-0
  • MF: C22H22FN3O2
  • MW: 379.427
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FAAH/cPLA2α-IN-1

FAAH/cPLA2α-IN-1 is a dual inhibitor of FAAH and cPLA2α with IC50s of 32 and 47 nM, respectively[1].

  • CAS Number: 1696401-38-3
  • MF: C19H26N4O5
  • MW: 390.43
  • Catalog: FAAH
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tigolaner

Tigolaner is a GABA antagonist that regulates chloride channel. Tigolaner is an antiparasitic agent[1].

  • CAS Number: 1621436-41-6
  • MF: C21H13ClF8N6O
  • MW: 552.81
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

SB 258719 hydrochloride

SB 258719 (hydrochloride) is a selective 5-HT7 receptor antagonist displayed high affnity (pKi=7.5) for the receptor. SB-258719 (hydrochloride) can be used for the research of cancer and neurological diseases[1][2].

  • CAS Number: 1217674-10-6
  • MF: C18H31ClN2O2S
  • MW: 374.97
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sparteine sulfate pentahydrate

(-)-Sparteine (sulfate) is a quinolizidine alkaloid that can be extracted from Lupinus. (-)-Sparteine (sulfate) inhibits the release of acetylcholine and has anticonvulsant effects[1].

  • CAS Number: 299-39-8
  • MF: C15H28N2O4S
  • MW: 332.46
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: 340.9ºC at 760mmHg
  • Melting Point: 135ºC
  • Flash Point: 148.3ºC

(S)-Salsolidine

(S)-Salsolidine is a weak monoamine oxidase (MAO) inhibitor (Ki=63 μM). The R enantiomer of Salsolidine is more potent than the S form (Ki=26 μM)[1].

  • CAS Number: 493-48-1
  • MF: C12H17NO2
  • MW: 207.27
  • Catalog: Monoamine Oxidase
  • Density: 1.034g/cm3
  • Boiling Point: 313.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 127.1ºC

1-[(4-hydroxyphenyl)methyl]-4-methoxyphenanthrene-2,7-diol

BChE-IN-11 (compound 10) is a potent, selective and non-competitive BChE (butyrylcholinesterase) inhibitor, with an IC50 of 2.1 μM. BChE-IN-11 can be used for Alzheimer's disease (AD) research[1].

  • CAS Number: 133740-30-4
  • MF: C22H18O4
  • MW: 346.37600
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Xanthotoxol

Xanthotoxol is a biologically active linear furocoumarin, shows strong pharmacological activities as anti-inflammatory, antioxidant, 5-HT antagonistic, and neuroprotective effects.

  • CAS Number: 2009-24-7
  • MF: C11H6O4
  • MW: 202.163
  • Catalog: 5-HT Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 428.1±45.0 °C at 760 mmHg
  • Melting Point: 250ºC
  • Flash Point: 212.7±28.7 °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