| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
D4 Receptor; 5-HT1A Receptor (pIC50 = 8.87); 5-HT1A Receptor (pA2 = 9.71)
|
|---|---|
| ln Vitro |
In vitro activity: WAY 100635 (10 nM) superfused dorsal raphe nucleus (DRN) slices causes most putative 5-HT neurons to fire at a rate of 13% above baseline. Moreover, 5-HT (3–15 μM), 8–OH–DPAT (10 nM), 5-carboxamidotryptamine (20 nM), and lesopitron (100 nM) all totally inhibit the reduction in firing rate that WAY 100635 causes. Increasing the concentration of 5-HT to 300 μM with an IC50 of 0.95 nM completely overcomes the antagonistic effect of WAY 100635. The membrane input resistance and resting membrane potential of intracellularly recorded CA1 pyramidal cells in hippocampal slices are not affected by WAY 100635 (0.5 nM–10 nM). WAY 100635, on the other hand, completely blocks both the hyperpolarization (IC50 = 1.3 nM) and the membrane input resistance decrease caused by 5-HT and 5-carboxamidotryptamine (IC50 = 22.5 μM and 50 nM, respectively).[1] WAY 100635 is > 100-fold selective for the 5-HT1A site in comparison to a variety of other CNS receptors, with an IC50 of 1.35 nM. Mn2+ can inhibit [3H]WAY 100635-specific binding, but not guanine nucleotides. The Bmax of [3H]WAY 100635 specific binding is consistently 50–60% greater than that of the agonist radioligand, [3H]8–OH-DPAT. Way 100635 does not act as a 5-HT1A receptor agonist; however, it dose-dependently inhibits the effects of agonists at the dorsal raphe 5-HT neurone and the postsynaptic 5-HT1A receptor in the CA1 region of the hippocampus. **[2]** [3H]. Its Kd is roughly 2.5 nM for WAY 100635.[3] At 0.3 nM, WAY 100635 exhibits an apparent pA2 value of 9.71, indicating its potency and insurmountable nature as a 5-HT1A receptor agonist in the isolated guinea-pig ileum.[4] The amount of tritium found in the entire brain only accounted for 1.5–1.8% of the injected radioactivity five minutes after the intravenous injection of [3H]WAY 100635 (4 μCi–7.6 μCi per mouse). Regional differences in 3H accumulation already correspond to those of 5-HT1A receptor density.[5] Conclusions from studies using WAY 100635 as a selective 5-HT1A antagonist may need to be reevaluated in light of its recently discovered dopaminergic activity.[6]
|
| ln Vivo |
[3H]WAY 100635 is demonstrated to bind specifically to 5-HT1A receptors in the brain after being given intravenously to mice. Additionally, WAY 100635 dose-dependently inhibits 8-OH-DPAT'scapacityto cause the "5-HT syndrome," hypothermia, hyperphagia, and an increase in plasma ACTH levels. This is achieved by inhibiting the firing of dorsal raphe 5-HT neurones. WAY 100635 produces anxiolytic-like effects in the mouse light/dark box anxiety model. In the delayed-matching-to-position model of rat short-term memory, WAY 100635 reverses the disruptive effects of 8-OH-DPAT on motor motivational performance but has no intrinsic effect on cognition.[2] In the anesthetized rat, WAY 100635 inhibits the inhibitory action of 8-OH-DPAT on dorsal raphe neuronal firing at doses that have no inherent inhibitory effect. In behavioral models, WAY 100635 does not directly cause any overt behavioral changes in rats or guinea pigs, but it effectively counteracts the behavioral syndrome caused by 8-OH-DPAT (minimum effective dose = 0.003 mg/kg s.c. and ID50 = 0.01 mg/kg s.c., respectively). With ID50 values of 0.01 mg/kg s.c., WAY 100635 also prevents the hypothermia that is brought on by 8-OH-DPAT in rats and mice.[4]
|
| Enzyme Assay |
Screening assays[6]
For the initial screens by the NIMH-PDSP at a large number of cloned receptors and transporters (for details, see Roth et al. (2002) and Shapiro et al. (2003)), 10 μM WAY-100635 was used. Where significant inhibition was measured (>50% inhibition with quadruplicate determinations), K i determinations were performed with 6–10 concentrations of unlabelled ligand, and data were analyzed with GraphPad Prism.
|
| Cell Assay |
Extracellular recordings are performed using glass microelectrodes that have been loaded with 2 M NaC1 (12 MΩ–15 MΩ). Two or three-millisecond biphasic action potentials, slow (0.5 Hz - 2.0 Hz) discharge patterns, and regular discharge patterns are characteristics that distinguish cells as 5-HT neurons. The alpha-l adrenergic agonist phenylephrine (3 μM) is added to the superfusing ACSF to cause firing in the otherwise silent neurons. Prior to applying the various medications, baseline activity is tracked for at least ten minutes. Precise action potentials coupled to an A/D converter and a PC drive individual action potentials that drive an oscilloscope, an electronic ratemeter, and a high-input impedance amplifier. The integrated firing rate is measured, calculated, and shown on a chart recorder as successive 10-sec samples using specialized software. Agonists' effects are assessed by comparing the mean discharge frequency recorded during the two minutes prior to WAY 100635 application with the frequency recorded at the peak of the drug's action, which is typically two to five minutes after application starts. The effect of the agonist is contrasted with the baseline firing rate and frequency observed during the antagonist's single superfusion when the agonists are applied in the presence of the antagonist. Before retesting the agonists' action, the antagonist is given ten to twenty-five minutes to acclimate.
|
| Animal Protocol |
Dissolved in 0.9% NaCl; 250 μL (30.4 μCi/mL); i.v. injection
Male CD1 mice with 25-30 g body weight
|
| References |
[1]. J Pharmacol Exp Ther . 1996 Aug;278(2):679-88. [2]. Behav Brain Res . 1996;73(1-2):337-53. [3]. Brain Res . 1997 Jan 16;745(1-2):96-108. [6]. Psychopharmacology (Berl). 2006 Oct;188(2):244-51. |
| Additional Infomation |
N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide is a member of piperazines.
|
| Molecular Formula |
C29H38N4O6
|
|---|---|
| Molecular Weight |
538.6352
|
| Exact Mass |
538.279
|
| CAS # |
634908-75-1
|
| Related CAS # |
WAY-100635;162760-96-5
|
| PubChem CID |
5684
|
| Appearance |
Typically exists as solid at room temperature
|
| Boiling Point |
594.8ºC at 760 mmHg
|
| Flash Point |
313.5ºC
|
| LogP |
3.54
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
31
|
| Complexity |
546
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])N(C1=C([H])C([H])=C([H])C([H])=N1)C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])N(C2=C([H])C([H])=C([H])C([H])=C2OC([H])([H])[H])C([H])([H])C1([H])[H].O([H])C(C([H])=C([H])C(=O)O[H])=O
|
| InChi Key |
SBPRIAGPYFYCRT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H34N4O2/c1-31-23-12-6-5-11-22(23)28-18-15-27(16-19-28)17-20-29(24-13-7-8-14-26-24)25(30)21-9-3-2-4-10-21/h5-8,11-14,21H,2-4,9-10,15-20H2,1H3
|
| Chemical Name |
N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexanecarboxamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8565 mL | 9.2826 mL | 18.5653 mL | |
| 5 mM | 0.3713 mL | 1.8565 mL | 3.7131 mL | |
| 10 mM | 0.1857 mL | 0.9283 mL | 1.8565 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
