WAY-100635 Maleate

N.º de catálogoS2663 Lote:S266301

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Datos técnicos

Fórmula

C25H34N4O2.C4H4O4
Peso molecular 538.64 Número CAS 1092679-51-0
Solubilidad (25°C)* In vitro DMSO 85 mg/mL (157.8 mM)
Ethanol 85 mg/mL (157.8 mM)
Water Insoluble
In vivo (Agregue los solventes al producto individualmente y en orden.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml significa ligeramente soluble o insoluble.
* Tenga en cuenta que Selleck prueba la solubilidad de todos los compuestos internamente, y la solubilidad real puede diferir ligeramente de los valores publicados. Esto es normal y se debe a ligeras variaciones entre lotes.
* Envío a temperatura ambiente (Las pruebas de estabilidad demuestran que este producto se puede enviar sin medidas de refrigeración.)

Preparación de soluciones madre

Actividad biológica

Descripción WAY-100635 Maleate is a potent and selective 5-HT receptor antagonist with IC50 of 0.95 nM.
Objetivos
5-HT
0.95 nM
In vitro In dorsal raphe nucleus (DRN) slices superfused with WAY 100635 (10 nM), the majority of putative 5-HT neurons increase their firing rate (13% of baseline rate). In addition, WAY 100635 completely prevents the decrease in firing rate produced by 5-HT (3-15 μM), 8-OH-DPAT (10 nM), 5-carboxamidotryptamine (20 nM) and lesopitron (100 nM). The antagonism exerted by WAY 100635 is fully surmounted by increasing the concentration of 5-HT to 300 μM with an IC50 of 0.95 nM. In hippocampal slices, WAY 100635 (0.5 nM -10 nM) does not alter the resting membrane potential or the membrane input resistance of intracellularly recorded CA1 pyramidal cells. However, WAY 100635 completely prevents not only the hyperpolarization, with an IC50 of 1.3 nM, but also the decrease in membrane input resistance produced by 5-HT and 5-carboxamidotryptamine with IC50 of 22.5 μM and 50 nM, respectively. WAY 100635 has an IC50 of 1.35 nM and is > 100-fold selective for the 5-HT1A site relative to a range of other CNS receptors. The Bmax of [3H]WAY 100635 specific binding is consistently 50-60% greater than that of the agonist radioligand, [3H]8-OH-DPAT. Mn2+, but not guanine nucleotides, inhibits [3H]WAY 100635-specific binding. WAY 100635 has no 5-HT1A receptor agonist actions, but dose-dependently blocks the effects of agonists at both the postsynaptic 5-HT1A receptor in the CA1 region of the hippocampus, and the somatodendritic 5-HT1A receptor locates on dorsal raphe 5-HT neurones. [3H]WAY 100635 has a Kd of approximately 2.5 nM. In the isolated guinea-pig ileum WAY 100635 is a potent and, at high concentrations, an insurmountable antagonist of the 5-HT1A receptor agonist action of 5-carboxamidotryptamine, with an apparent pA2 value (at 0.3 nM) of 9.71. Five minutes after the i.v. injection of [3H]WAY 100635 (4 μCi -7.6 μCi per mouse) the amount of tritium found in the whole brain only accounted for 1.5-1.8% of the injected radioactivity, regional differences in 3H accumulation already correspondes to those of 5-HT1A receptor density. In light of its only recently discovered dopaminergic activity, conclusions drawn from studies that employs WAY 100635 as a selective 5-HT1A antagonist may need to be re-evaluated.
In vivo [3H]WAY 100635 is shown to bind selectively to brain 5-HT1A receptors, following intravenous administration to mice. WAY 100635 also dose-dependently blocks the ability of 8-OH-DPAT to inhibit the firing of dorsal raphe 5-HT neurones, and to induce the '5-HT syndrome', hypothermia, hyperphagia and to elevate plasma ACTH levels. In the mouse light/dark box anxiety model, WAY 100635 induces anxiolytic-like effects. WAY 100635 has no intrinsic effect on cognition in the delayed-matching-to-position model of short-term memory in the rat, but reverses the disruptive effects of 8-OH-DPAT on motor motivational performance. WAY 100635 blocks the inhibitory action of 8-OH-DPAT on dorsal raphe neuronal firing in the anaesthetised rat at doses which has no inhibitory action per se. In behavioural models, WAY 100635 itself induces no overt behavioural changes but potently antagonises the behavioural syndrome induced by 8-OH-DPAT in the rat and guinea-pig (minimum effective dose = 0.003 mg/kg s.c. and ID50 = 0.01 mg/kg s.c., respectively). WAY 100635 also blocks the hypothermia induced by 8-OH-DPAT in the mouse and rat with ID50 values of 0.01 mg/kg s.c.
Características Caracterizado como el primer radioligando antagonista 5-HT1A.

Protocolo (de referencia)

Ensayo celular:

[1]
  • Líneas celulares

    Neurons

  • Concentraciones

    1 nM -5 nM

  • Tiempo de incubación

    2 minutes -5 minutes

  • Método

    Extracellular recordings are made with glass microelectrodes filled with 2 M NaC1 (12 MΩ-15 MΩ). Cells are identified as 5-HT neurons according to the following criteria: biphasic action potentials of 2 msec to 3 msec in duration, slow (0.5 Hz - 2.0 Hz) and regular pattern of discharge. Firing is evoked in the otherwise silent neurons by adding the alpha-l adrenergic agonist phenylephrine (3 μM) to the superfusing ACSF. Baseline activity is recorded for at least 10 minutes before application of the different drugs. The electric signals are fed into a high-input impedance amplifier, an oscilloscope and an electronic ratemeter triggered by individual action potentials connected to an A/D converter and a personal computer. Using dedicated software, the integrated firing rate is recorded, computed and displayed on a chart recorder as consecutive 10-sec samples. The effects of agonists are evaluated by comparing the mean discharge frequency recorded during the 2 minutes that preceded WAY 100635 application with that recorded at the peak of WAY 100635 action (usually 2-5 minutes after the beginning of application). When the agonists are applied in the presence of the antagonist, the effect of the agonist is compared to baseline firing rate and to the frequency recorded during superfusion of the antagonist alone. The antagonist is left to equilibrate for 10 minutes to 25 minutes before retesting of the action of agonists.
Estudio en animales:

[2]
  • Modelos animales

    Male CD1 mice with 25-30 g body weight

  • Dosificaciones

    250 μL (30.4 μCi/mL)

  • Administración

    Administered via i.v.

Referencias

  • https://pubmed.ncbi.nlm.nih.gov/8768719/
  • https://pubmed.ncbi.nlm.nih.gov/8788530/
  • https://pubmed.ncbi.nlm.nih.gov/9037397/
  • https://pubmed.ncbi.nlm.nih.gov/8566121/
  • https://pubmed.ncbi.nlm.nih.gov/7705451/

Validación de productos por parte del cliente

<p>Effects of antagonists on the anti-hyperalgesic effects of sinomenine in CCI rats. * P , 0.05 as compared to vehicle control group (N=8 per group). The 5-HT1A receptor antagonist WAY100635 does not block the antinociceptive effects of 40 mg/kg sinomenine.</p>

, , Sci Rep, 2014, 4:7270.

The effects of D1 antagonist Sch23390 and 5-HT1A antagonist WAY-100635 on CK’s antidepressant behavioral effects. Sch23390 (0.05 mg/kg) or WAY-100635 (0.2 mg/kg) was administered (s.c.) 30 min before CK once daily for consecutive 14 days, and TST (a) was performed on day 13, FST (b) on day 14. For CUMS model study, after 2 weeks of CUMS, the antagonists were administrated respectively for 4 weeks, and then sucrose preference (c) and open field test (d) were performed. FST chronic forced swimming test, TST tail suspension test. Data represent means ± SEM (n = 12/group). *p < 0.05, **p < 0.01, one-way ANOVA with post-hoc Tukey’s HSD test or Dunnett’s t test; #p < 0.05, two-way repeated-measures ANOVA interaction.

Datos de [ , , Neurochem Res, 2018, 43(7):1371-1382 ]

Selleck's WAY-100635 Maleate Ha sido citado por 15 Publicaciones

Levo-Tetrahydroberberrubine Produces Anxiolytic-Like Effects in Mice through the 5-HT1A Receptor [ PLoS One, January 13, 2017, e0168964] PubMed: 28085967
N-Demethylsinomenine, an active metabolite of sinomenine, attenuates chronic neuropathic and inflammatory pain in mice [ Scientific Reports, April 29, 2021, 9300] PubMed: 33927244
Regular Aerobic Exercise Attenuates Pain and Anxiety in Mice by Restoring Serotonin-Modulated Synaptic Plasticity in the Anterior Cingulate Cortex [ Medicine & Science in Sports & Exercise, April 1, 2022, 566-581] PubMed: 34935710
Single-dose psilocybin rapidly and sustainably relieves allodynia and anxiodepressive-like behaviors in mouse models of chronic pain [ Nat Neurosci, 2025, 28(11):2285-2295] PubMed: 41039182
Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension [ Gastroenterology, 2024, 167(5):993-1007] PubMed: 38906512
Regular Aerobic Exercise Attenuates Pain and Anxiety in Mice by Restoring Serotonin-Modulated Synaptic Plasticity in the Anterior Cingulate Cortex [ Med Sci Sports Exerc, 2022, 54(4):566-581] PubMed: 34935710
Regular Aerobic Exercise Attenuates Pain and Anxiety in Mice by Restoring Serotonin-Modulated Synaptic Plasticity in the Anterior Cingulate Cortex [ Medicine & Science in Sports & Exercise, 2022, 566-581] PubMed: 34935710
N-Demethylsinomenine, an active metabolite of sinomenine, attenuates chronic neuropathic and inflammatory pain in mice [ Scientific Reports, 2021, 9300] PubMed: 33927244
N-Demethylsinomenine, an active metabolite of sinomenine, attenuates chronic neuropathic and inflammatory pain in mice [ Sci Rep, 2021, 11(1):9300] PubMed: 33927244
Spinal Serotonin 1A Receptor Contributes to the Analgesia of Acupoint Catgut Embedding by Inhibiting Phosphorylation of the N-Methyl-d-Aspartate Receptor GluN1 Subunit in Complete Freund's Adjuvant-Induced Inflammatory Pain in Rats [Cui WQ, et al. J Pain, 2019, 20(1):16.e1-16.e16] PubMed: 30102991

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