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.


Anti-infection >
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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Zimeldine

Zimelidine is a potent and selective inhibitor of serotonin 5-HT uptake and SERT. Zimelidine is an antidepressant[1][2][3][4].

  • CAS Number: 56775-88-3
  • MF: C16H19BrCl2N2
  • MW: 317.224
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 412.8±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 203.4±28.7 °C

17-Beta-Estradiol-3-O-Sulfate Sodium

17β-Estradiol sulfate (sodium), also known as β-Estradiol 3-sulfate sodium salt, is a neuroactive steroid[1][2].

  • CAS Number: 4999-79-5
  • MF: C18H23NaO5S
  • MW: 374.427
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Riluzole hydrochloride

Riluzole hydrochloride is an anticonvulsant drug and belongs to the family of use-dependent Na+ channel blocker which can also inhibit GABA uptake with an IC50 of 43 μM.

  • CAS Number: 850608-87-6
  • MF: C8H6ClF3N2OS
  • MW: 270.659
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Promazine hydrochloride

Promazine (hydrochloride) is a D2 dopamine receptor antagonist, belongs to the phenothiazine class of antipsychotics, used to treat schizophrenia.

  • CAS Number: 53-60-1
  • MF: C17H21ClN2S
  • MW: 320.88000
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 412.7ºC at 760mmHg
  • Melting Point: 174-176ºC
  • Flash Point: 203.4ºC

AGROCLAVIN

Agroclavine is a natural, clavine type of ergot alkaloid. Agroclavine is a D1 dopamine receptor and α1-adrenoceptor agonist. Agroclavine also has anticancer and antimicrobial activities[1][2].

  • CAS Number: 548-42-5
  • MF: C16H18N2
  • MW: 238.32800
  • Catalog: Adrenergic Receptor
  • Density: 1.161g/cm3
  • Boiling Point: 422.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 209.3ºC

Galantamine

Galanthamine is a potent acetylcholinesterase (AChE) inhibitor with an IC50 of 500 nM.

  • CAS Number: 357-70-0
  • MF: C17H21NO3
  • MW: 287.353
  • Catalog: AChE
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 439.3±45.0 °C at 760 mmHg
  • Melting Point: 119-121ºC
  • Flash Point: 219.5±28.7 °C

BChE-IN-20

BChE-IN-20 (compound 7c) is a highly potent BChE-selective inhibitor and exhibits IC50s of 105 and 2.3 nM for eqBChE and hBChE, respectively. BChE-IN-20 inhibits P glycoprotein with IC50 of 0.27 μM. BChE-IN-20 is a promising template to improve design and development of BChE-selective ligands of pharmaceutical interest, including inhibitors and fluorogenic probes.

  • CAS Number: 1428439-79-5
  • MF: C27H39N5O2
  • MW: 465.63
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Org 25935

Org 25935 is a potent and selective glycine transporter 1 protein (GlyT1) inhibitor with an IC50 value of 100 nM. Org 25935 can decrease ethanol (EtOH) intake and EtOH preference in rats, whereas water intake is unaffected. Org 25935 can be used for researching alcohol dependence or abuse[1].

  • CAS Number: 949588-40-3
  • MF: C21H26ClNO3
  • MW: 375.89
  • Catalog: GlyT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Umibecestat

Umibecestat (CNP520) is a beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibitor with IC50s of 11 nM and 10 nM for human BACE-1 and mouse BACE-1, respectively[1].

  • CAS Number: 1387560-01-1
  • MF: C19H15ClF7N5O2
  • MW: 513.80
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propiverine hydrochloride

Propiverine hydrochloride is a bladder spasmolytic with calcium antagonistic and anticholinergic properties. Propiverine hydrochloride can be used for the research of overactive blaqdder and urinary incontinence[1][2].

  • CAS Number: 54556-98-8
  • MF: C23H30ClNO3
  • MW: 403.942
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 494.7ºC at 760 mmHg
  • Melting Point: 213-216ºC
  • Flash Point: 253ºC

Zotepine

Zotepine, an antipsychotic agent, is a potent antagonist of 5-HT2A, 5-HT2C, Histamine H1, α1-adrenergic and Dopamine D2 receptors, with Kds of 2.6 nM, 3.2 nM, 3.3 nM, 7.3 nM and 8 nM, respectively. Zotepine exhibits antidepressive and anxiolytic effects in vivo[1][2].

  • CAS Number: 26615-21-4
  • MF: C18H18ClNOS
  • MW: 331.86
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 478.4±45.0 °C at 760 mmHg
  • Melting Point: 90-91 °C
  • Flash Point: 243.2±28.7 °C

(RS)-AMPA monohydrate

(RS)-AMPA ((±)-AMPA) monohydrate is a glutamate analogue and a potent and selective excitatory neurotransmitter L-glutamic acid agonist. (RS)-AMPA monohydrate does not interfere with binding sites for kainic acid or NMDA receptors[1][2].

  • CAS Number: 76463-67-7
  • MF: C7H12N2O5
  • MW: 204.18
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RJR-2403

Rivanicline (RJR-2403) is a neuronal nicotinic receptor agonist, showing high selectivity for the α4β2 subtype (Ki=26 nM); > 1,000 fold selectivity than α7 receptors(Ki= 36000 nM).IC50 value: 26 nM [1]Target: α4β2 nAChRin vitro: At concentrations up to 1 mM, Rivanicline does not significantly activate nAChRs in PC12 cells, muscle type nAChRs or muscarinic receptors. Dose-response curves for agonist-induced ileum contraction indicate that Rivanicline is less than one-tenth as potent as nicotine with greatly reduced efficacy. Rivanicline does not antagonize nicotine-stimulated muscle or ganglionic nAChR function (IC50 > 1 mM). Chronic exposure of M10 cells to Rivanicline (10 microM) results in an up-regulation of high-affinity nAChRs phenomenologically similar to that seen with nicotine [1].in vivo: Rivanicline significantly improved passive avoidance retention after scopolamine-induced amnesia and enhanced both working and reference memory in rats with ibotenic acid lesions of the forebrain cholinergic projection system in an 8-arm radial maze paradigm. By comparison, Rivanicline was 15 to 30-fold less potent than nicotine in decreasing body temperature, respiration, Y-maze rears and crosses and acoustic startle response [2]. Metanicotine was about 5-fold less potent than nicotine in the tail-flick test after s.c administration, but slightly more potent after central administration [3].

  • CAS Number: 15585-43-0
  • MF: C10H14N2
  • MW: 162.23200
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Substance P (1-7)

Substance P (7-11) is a fragment of the neuropeptide, substance P (SP). Substance P (7-11) gives depressor and bradycardic effects when applied to the nucleus tractus solitarius.

  • CAS Number: 68060-49-1
  • MF: C41H65N13O10
  • MW: 900.03600
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pumosetrag Hydrochloride

Pumosetrag Hydrochloride (MKC-733; DDP-733) is an orally available 5-HT3 partial agonist developed for the treatment of irritable bowel syndrome and gastroesophageal reflux disease.

  • CAS Number: 194093-42-0
  • MF: C15H18ClN3O2S
  • MW: 339.840
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 529.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 274.3ºC

TIM-063

TIM-063 (TIM063) is a potent, selective, ATP-competitive CaMKK inhibitor with Ki of 0.35/0.2 uM for CaMKKα and CaMKKβ, respectively.TIM-063 directly targets the catalytic domain of CaMKK, similar to STO-609.TIM-063 suppressed the ionomycin-induced phosphorylation of exogenously expressed CaMKI, CaMKIV, and endogenous AMPKα in HeLa cells with an IC50 of 0.3 uM.TIM-063 suppressed CaMKK isoform-mediated CaMKIV phosphorylation in transfected COS-7 cells.TIM-063 displayed cell permeability and the ability to inhibit CaMKK activity in cells. TIM-063 is a useful chemical probe for the precise analysis of CaMKK-mediated signaling pathways.

  • CAS Number: 2493978-38-2
  • MF: C18H9N3O4
  • MW: 331.287
  • Catalog: CaMK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deltorphin I TFA

Deltorphin I is a δ-opioid receptor agonist with high affinity and selectivity.

  • CAS Number: 122752-15-2
  • MF: C37H52N8O10
  • MW: 768.85600
  • Catalog: Peptides
  • Density: 1.284g/cm3
  • Boiling Point: 1242.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 705.2ºC

Fenclonine

4-Chloro-L-phenylalanine (L-PCPA) is a 5-HT biosynthesis inhibitor. 4-Chloro-L-phenylalanine is also a nonspecific antagonist of both isoforms of tryptophan hydroxylase (TPH1 and TPH2)[1].

  • CAS Number: 14173-39-8
  • MF: C9H10ClNO2
  • MW: 199.634
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 339.5±32.0 °C at 760 mmHg
  • Melting Point: 235-238ºC
  • Flash Point: 159.1±25.1 °C

LY43578

LY43578 is an orally active aromatase inhibitor. LY43578 inhibits P-450-dependent p-nitroanisole O-demethylation and ethylmorphine N-demethylation in hepatic microsomes isolated from rat, with the IC50 of 0.3 and 5 μΜ, respectively. LY43578 can be used for neurological disorder study[1][2].

  • CAS Number: 26766-35-8
  • MF: C17H12Cl2N2O
  • MW: 331.20
  • Catalog: Cytochrome P450
  • Density: 1.376g/cm3
  • Boiling Point: 494.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 253.1ºC

Netupitant

Netupitant (CID-6451149) is a highly potent and selective, orally active neurokinin-1 receptor antagonist with Ki of 0.95 nM.IC50 value: 0.95 nM (Ki) [1]Target: NK1 receptorin vitro: Netupitant also dose-dependently inhibited the SP response as expected from an NK1 receptor antagonist. Importantly, when both palonosetron and netupitant were present, they exhibited an enhanced inhibition of the SP response compared to either of the two antagonists alone [2].in vivo: In mice the intrathecal injection of SP elicited the typical scratching, biting and licking response that was dose-dependently inhibited by Netupitant given intraperitoneally in the 1-10mg/kg dose range. In gerbils, foot tapping behavior evoked by the intracerebroventricular injection of a NK(1) agonist was dose-dependently counteracted by Netupitant given intraperitoneally (ID(50) 1.5mg/kg) or orally (ID(50) 0.5mg/kg) [3].

  • CAS Number: 290297-26-6
  • MF: C30H32F6N4O
  • MW: 578.592
  • Catalog: Neurokinin Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 597.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 315.1±30.1 °C

Levetimide

Levetimide is a potent and stereoselective inhibitor of [3H](+)pentazocine binding, with a Ki of 2.2 nM[1].

  • CAS Number: 21888-99-3
  • MF: C23H26N2O2
  • MW: 362.46500
  • Catalog: mAChR
  • Density: 1.178g/cm3
  • Boiling Point: 543.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 282.7ºC

BChE-IN-17

BChE-IN-17 (compound 6n) is a potent and selective BChE inhibitor with IC50s of 10.5 nM and 32.5 nM for eqBChE and hBChE, respectively. BChE-IN-17 shows over 1000-fold selectivity to BChE against AChE. BChE-IN-17 shows low neurotoxicity and moderate neuroprotective effects[1].

  • CAS Number: 2425632-57-9
  • MF: C23H23BrN2O4S2
  • MW: 535.47
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NKP608

NKP608 is a non-peptidic derivative of 4-aminopiperidine which acts as a selective, specific and potent antagonist at the neurokinin-1 (NK-1) receptor both in vitro(IC50=2.6 nM) and in vivo. IC50 value: 2.6 nMTarget: NK-1 receptorIn vitro, the binding of NKP608 to bovine retina was characterized by an IC50 of 2.6+/-0.4 nM, whereas the compound's affinity to other receptor binding sites, including NK-2 and NK-3, was much lower. Species differences in IC(50) values with NKP608 were less pronounced than with previously described NK-1 receptor antagonists, being 13+/-2 and 27+/-2 nM in gerbil midbrain and rat striatum, respectively. In vivo, using the hind foot thumping model in gerbils, NKP608 exhibited a potent NK-1 antagonistic activity following oral administration (ID(50)=0.23 mg/kg; 2 h pretreatment), supporting a central activity of NKP608. NKP608 may prove a useful anxiolytic compound.

  • CAS Number: 177707-12-9
  • MF: C31H24ClF6N3O2
  • MW: 619.985
  • Catalog: Neurokinin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 719.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 388.8±32.9 °C

Nelonicline

Nelonicline (ABT-126) is a selective neuronal nicotinic receptor agonist.

  • CAS Number: 1026134-63-3
  • MF: C17H19N3OS
  • MW: 313.417
  • Catalog: nAChR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 460.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 232.1±31.5 °C

TVP1022

TVP1022 is the S-isomer of rasagiline, which is an anti-Parkinson drug, appears to have the same neuroprotective activity as the R-isomer, but is 1000-fold less active as an MAO-B inhibitor.

  • CAS Number: 185517-74-2
  • MF: C12H13N
  • MW: 171.23800
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pro-Leu-Gly-NH2

MIF-1 (Melanostatin), an endogenous brain peptide, is a potent dopamine receptor allosteric modulator. MIF-1 inhibits melanin formation. MIF-1 blocks the effects of opioid receptor activation to modulate the analgesic effects of morphine and stress-induced analgesia (SIA). MIF-1 accesses from the blood to the CNS by directly crossing the blood-brain barrier (BBB)[1][2][3].

  • CAS Number: 2002-44-0
  • MF: C13H24N4O3
  • MW: 284.35500
  • Catalog: Dopamine Receptor
  • Density: 1.147g/cm3
  • Boiling Point: 626.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 332.5ºC

FG 7142

FG 7142 (ZK 39106; LSU-65), a non-selectively benzodiazepine inverse agonist, has high affinity for the α1 subunit-containing GABAA receptor (Ki=91 nM). FG 7142 (ZK 39106; LSU-65) also modulates GABA-induced chloride flux at GABAA receptors expressing the α1 subunit (EC50= 137 nM). FG 7142 (ZK 39106; LSU-65) can increase tyrosine hydroxylation and cause upregulation of β-adrenoceptors in mouse cerebral cortex[1].

  • CAS Number: 78538-74-6
  • MF: C13H11N3O
  • MW: 225.24600
  • Catalog: GABA Receptor
  • Density: 1.328g/cm3
  • Boiling Point: 576.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 302.3ºC

Sulpiride

Sulpiride is a D2 receptor a antagonist, an atypical antipsychotic drug of the benzamide class, used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and sometimes used in low dosage to treat anxiety and mild depression.

  • CAS Number: 15676-16-1
  • MF: C15H23N3O4S
  • MW: 341.426
  • Catalog: Dopamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 180 - 185ºC
  • Flash Point: N/A

(RS)-(Tetrazol-5-yl)glycine

(RS)-(Tetrazol-5-yl)glycine (D,L-(tetrazol-5-yl)glycine) is a highly potent and selective N-methyl-D-aspartate (NMDA) receptor agonist[1]. (RS)-(Tetrazol-5-yl)glycine has EC50s of 99 nM, 1.7 μM for GluN1/GluN2D and GluN1/GluN2A, respectively[2]. (RS)-(Tetrazol-5-yl)glycine induces seizure responses and Fos in mice[3].

  • CAS Number: 138199-51-6
  • MF: C3H5N5O2
  • MW: 143.10400
  • Catalog: iGluR
  • Density: 1.804 g/cm3
  • Boiling Point: 447.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 224.2ºC

Fluphenazine (dihydrochloride)

Fluphenazine dihydrochloride is a phenothiazine-class D1DR and D2DR inhibitor; used to deliver Fluphenazine to biological systems in studies probing the effects and metabolic fates of this commonly used dopamine antagonist.

  • CAS Number: 146-56-5
  • MF: C22H28Cl2F3N3OS
  • MW: 510.44300
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 568.3ºC at 760mmHg
  • Melting Point: 200-202ºC
  • Flash Point: 297.5ºC