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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Ladostigil

Ladostigil (TV-3326) is a dual inhibitor of cholinesterase and brain-selective monoamine oxidase (MAO), with an IC50 of 37.1 and 31.8 μM for MAO-B and AChE, reapectively. Ladostigil could increase cholinergic transmission, prevent the formation of ROS or their actions and be used for the research of depression and Alzheimer's disease[1][2].

  • CAS Number: 209394-27-4
  • MF: C16H20N2O2
  • MW: 272.34200
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

hCAI/II-IN-5

hCAI/II-IN-5 (compound MZ8) is a potent hCA I and hCA II (human carbonic anhydrase isoenzymes I and II) inhibitor, with IC50 values of 37.88 and 45.23 nM, respectively. hCAI/II-IN-5 also shows inhibition profile against α-Glycosidase and AChE, with IC50 values of 48.98 and 420.14 nM, respectively. hCAI/II-IN-5 can be used for the research of many diseases such as diabetes, Alzheimer’s disease, heart failure, ulcer, and epilepsy[1].

  • CAS Number: 2428389-67-5
  • MF: C21H18Cl2N8O4S2
  • MW: 581.45
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dizocilpine

Dizocilpine, a potent anticonvulsant, is a selective and non-competitive NMDA receptor antagonist, with a Kd of 37.2 nM in rat brain membranes. Dizocilpine acts by binding to a site located within the NMDA associated ion channel and thus prevents Ca2+ flux[1][2].

  • CAS Number: 77086-21-6
  • MF: C16H15N
  • MW: 221.29700
  • Catalog: iGluR
  • Density: 1.144±0.06 g/cm3
  • Boiling Point: 320.3±11.0 °C
  • Melting Point: 68.75 ºC
  • Flash Point: N/A

SB-612111

SB-612111 is a novel and potent human opiate receptor-like orphan receptor (ORL-1) antagonist with a high affinity for hORL-1 (Ki=0.33 nM). SB-612111 exhibits selectivity for μ-, κ- and δ-receptors with Ki values of 57.6 nM, 160.5 nM and 2109 nM, respecticely. SB-612111 effectively antagonizes the pronociceptive action of Nociceptin (HY-P0183) in an acute pain model[1].

  • CAS Number: 371980-98-2
  • MF: C24H29Cl2NO
  • MW: 454.86000
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-O-Methyl Tolcapone

3-O-Methyltolcapone (Ro 40-7591) is a metabolite of Tolcapone. Tolcapone is an orally active, reversible, selective and potent COMT inhibitor. Tolcapone crosses the blood-brain barrier, and can be used for treatment of Parkinson's disease[1][2].

  • CAS Number: 134612-80-9
  • MF: C15H13NO5
  • MW: 315.32100
  • Catalog: COMT
  • Density: 1.317g/cm3
  • Boiling Point: 474.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 240.9ºC

BQCA

BQCA a highly selective allosteric modulator of the M1 mAChR.

  • CAS Number: 338747-41-4
  • MF: C18H15NO4
  • MW: 309.316
  • Catalog: mAChR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 492.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 251.7±28.7 °C

Clozapine

Clozapine (HF 1854) is an antipsychotic used to treat schizophrenia. Clozapine is a potent antagonist of dopamine and a number of other receptors, with a Ki of 9.5 nM for M1 receptor.

  • CAS Number: 5786-21-0
  • MF: C18H19ClN4
  • MW: 326.823
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 489.2±55.0 °C at 760 mmHg
  • Melting Point: 182-185°C
  • Flash Point: 249.6±31.5 °C

CP-409092 hydrochloride

CP-409092 hydrochloride is a partial agonist of GABAA receptor, with anti-anxiety activity[1].

  • CAS Number: 225240-86-8
  • MF: C17H20ClN3O2
  • MW: 333.81
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-Muscarine (chloride)

Muscarine ((+)-Muscarine) chloride is a toxin that can stimulate the parasympathetic nervous system. Muscarine is a prototype muscarinic acetylcholine receptor agonist[1][2].

  • CAS Number: 2303-35-7
  • MF: C9H20ClNO2
  • MW: 209.71400
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNJ-37822681 dihydrochloride

JNJ-37822681 dihydrochloride is a potent, specific, centrally active, fast-dissociating dopamine D2 receptor antagonist with a moderate binding affinity for the dopamine D2L receptor (Ki =158 nM), which has potential for the treatment of schizophrenia and bipolar disorder[1].

  • CAS Number: 2108806-02-4
  • MF: C17H19Cl2F5N4
  • MW: 445.26
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GluN2B receptor modulator-1

GluN2B receptor modulator-1 is a selective GluN2B negative allosteric modulator with an IC50 value of 31 nM.

  • CAS Number: 2222010-71-9
  • MF: C17H15F3N4O2S
  • MW: 396.39
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AChE-IN-20

AChE-IN-20 (compound M26) is a potent AChE inhibitor with IC50 value of 397.32 nM and with Ki value of 335.76 nM. AChE-IN-20 shows inhibition potency against hCA I , hCA II and α-GLY with IC50 values of 84.14, 69.24 and 52.08 nM and with Ki values of 97.86, 76.23 and 57.93 nM, respectively[1].

  • CAS Number: 2428389-65-3
  • MF: C22H20N8O6S2
  • MW: 556.57
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Xilmenolone

Xilmenolone is a GABAA receptor positive allosteric modulator[1].

  • CAS Number: 2368807-26-3
  • MF: C26H37N3O2
  • MW: 423.59
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Clebopride (malate)

Clebopride malate is a dopamine antagonist drug with antiemetic and prokinetic properties used to treat functional gastrointestinal disorders. Target: dopamineClebopride is a substituted benzamide, closely related to metoclopramide.

  • CAS Number: 57645-91-7
  • MF: C24H30ClN3O7
  • MW: 507.96400
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 514.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 265.1ºC

Mesdopetam hemitartrate

Mesdopetam (IRL790) hemitartrate is a dopamine D3 receptor antagonist (Ki=90 nM; IC50=9.8 μM for human recombinant D3 receptor) with psychomotor stabilizing properties. Mesdopetam hemitartrate is used for the research of motor and psychiatric complications in Parkinson disease[1][2].

  • CAS Number: 2562346-14-7
  • MF: C12H18FNO3S.1/2C4H6O6
  • MW: 700.77
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S26131

S26131 (compound 5) is a potent and selective MT1 melatoninergic ligand, and the Ki values are 0.5 and 112 nM for MT1 and MT2, respectively. S26131 behaves as an MT1 and MT2 antagonist[1].

  • CAS Number: 296280-56-3
  • MF: C31H34N2O4
  • MW: 498.61
  • Catalog: Melatonin Receptor
  • Density: 1.168±0.06 g/cm3(Predicted)
  • Boiling Point: 804.6±65.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Baclofen

Baclofen is a gamma-amino-butyric acid (GABA) derivative used as a skeletal muscle relaxant.Target: GABA ReceptorBaclofen, a lipophilic analog of gamma-aminobutyric acid, is clinically used to control spasticity. Baclofen pretreatment (3 mg/kg) not only prolonged the time taken for animals to reach a core body temperature of 40 degrees C (P < 0.001), but also reduced the percentage of rats attaining a core body temperature of 40 degrees C [1]. Baclofen overdose may result in coma, apnea, autonomic disturbances, cardiac conduction abnormalities, and seizures. Levels obtained shortly after overdose correlate with length of mechanical ventilation [2].

  • CAS Number: 1134-47-0
  • MF: C10H12ClNO2
  • MW: 213.661
  • Catalog: GABA Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 364.3±32.0 °C at 760 mmHg
  • Melting Point: 208-210°C
  • Flash Point: 174.1±25.1 °C

JNJ-18038683

JNJ-18038683 is a 5-Hydroxytryptamine Type 7 (5-HT7) receptor antagonist, with pKis of 8.19, 8.20 for rat and human 5-HT7 in HEK293 cells, respectively.

  • CAS Number: 851376-05-1
  • MF: C26H28ClN3O7
  • MW: 529.97
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RU 24969

RU 24969 is a selective agonist at the 5-HT1A and 5-HT1B receptors; IC50 value:Target: 5-HT1A/1B agonistRU 24969 possesses preference for the purported 5-HT1B subtype of central 5-HT1 recognition site. The reported significant linear correlation between hypotensive activity following intravenous (i.v.) administration to anesthetized rats and affinity for the central 5-HT1 binding site could only be maintained by incorporation of the affinity of RU 24969 for its low and 8-OH-DPAT for its high affinity binding site [1]. The drug RU 24969 (10 mg/kg) inhibited the rate of synthesis of 5-HT in rat brain by about 50%. Pretreatment of rats with desmethylimipramine over a longer term or clenbuterol given acutely, treatments known to enhance the behavioural responses of rats to various other 5-HT agonists, did not alter the RU 24969-induced response [2]. RU 24969 (0.03-3.0mg/kg, s.c.) dose-dependently decreased water consumption in water deprived rats [3].

  • CAS Number: 66611-26-5
  • MF: C14H16N2O
  • MW: 228.29000
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3β-Hydroxy-lup-20(29)-en-16-one

3β-Hydroxy-lup-20(29)-en-16-one (compound 9) is a dual inhibitor of AChE and BChE, with selectivity for BChE (IC50: 28.9 μM)[1].

  • CAS Number: 65043-60-9
  • MF: C30H48O2
  • MW: 440.70
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMY 14802 hydrochloride

BMY-14802 hydrochloride (BMY-14802-1) is a selective and orally active sigma receptor antagonist with an IC50 of 112 nM. BMY-14802 hydrochloride is also a 5-HT1A and adrenergic α1 receptors agonist. BMY-14802 hydrochloride has antipsychotic effects[1][2][3].

  • CAS Number: 105565-55-7
  • MF: C18H23ClF2N4O
  • MW: 384.85100
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 520.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 268.8ºC

Alaproclate HCl

Alaproclate (GEA 654) hydrochloride is a selective and orally active serotonin re-uptake inhibitor (SSRI). Alaproclate hydrochloride also acts as a potent, reversible and noncompetitive antagonist of the NMDA receptor coupled ion flow[1][2].

  • CAS Number: 60719-83-7
  • MF: C13H19Cl2NO2
  • MW: 292.20
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 324.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 150.2ºC

Mecamylamine-d3 hydrochloride

Mecamylamine-d3 hydrochloride is the deuterium labeled Mecamylamine hydrochloride. Mecamylamine hydrochloride is an orally active, nonselective, noncompetitive nAChR antagonist that can treat various neuropsychiatric disorders. Mecamylamine hydrochloride is originally used as a ganglionic blocker in treating hypertension. Mecamylamine hydrochloride can easily crosses the blood-brain barrier[1][2].

  • CAS Number: 1217625-71-2
  • MF: C11H19ClD3N
  • MW: 206.77100
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aptiganel hydrochloride

Aptiganel hydrochloride (Cerestat) is a non-competitive NMDA receptor antagonist with neuroprotective effect.

  • CAS Number: 137160-11-3
  • MF: C20H22ClN3
  • MW: 303.401
  • Catalog: iGluR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 490.9±38.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 250.7±26.8 °C

UCM-1306

UCM-1306 is a potent and orally active human dopamine D1 receptor allosteric modulator (PAM). UCM-1306 increases the endogenous dopamine (DA) maximal effect both in human and mouse D1 receptors. UCM-1306 not only for improving motor symptoms but also for addressing the key comorbid cognitive impairment associated with long-term Parkinson’s disease (PD)[1].

  • CAS Number: 2258608-78-3
  • MF: C14H14FNO2S
  • MW: 279.33
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DAU 5884 hydrochloride

DAU 5884 hydrochloride is a potent muscarinic M3 receptor antagonist. DAU 5884 hydrochloride inhibits methacholine-dependent effects on cell proliferation and muscle contractility[1].

  • CAS Number: 131780-48-8
  • MF: C17H22ClN3O3
  • MW: 351.83
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 463 °C
  • Melting Point: N/A
  • Flash Point: N/A

(+)-MK 801 Maleate

(+)-MK 801 Maleate is a potent, selective and non-competitive NMDA receptor antagonist with Kd of 37.2 nM in rat brain membranes.

  • CAS Number: 77086-22-7
  • MF: C20H19NO4
  • MW: 337.369
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: 541ºC at 760 mmHg
  • Melting Point: 183-185ºC
  • Flash Point: 281ºC

BChE-IN-10

BChE-IN-10 (compound 6) is a potent butyrylcholinesterase (BChE) mixed-type inhibitor with an IC50 value of 6.4 μM. BChE-IN-10 can be isolated from Bletilla striata. BChE-IN-10 can be used for the research of Alzheimer's disease (AD)[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Flumazenil acid

Flumazenil acid is a metabolite of Flumazenil[1]. Flumazenil is a GABAA receptor antagonist[2].

  • CAS Number: 84378-44-9
  • MF: C13H10FN3O3
  • MW: 275.24
  • Catalog: GABA Receptor
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 570.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 298.8±30.1 °C

Propofol

Propofol potently and directly activates GABAA receptor and inhibits glutamate receptor mediated excitatory synaptic transmission. Propofol has antinociceptive properties and is used for sedation and hypnotic[1].

  • CAS Number: 2078-54-8
  • MF: C12H18O
  • MW: 178.271
  • Catalog: GABA Receptor
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 256.0±0.0 °C at 760 mmHg
  • Melting Point: 18 °C(lit.)
  • Flash Point: 107.5±7.2 °C