| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
Dopamine D2 autoreceptor (primary), D3 receptor (functional selectivity), D4 receptor, and 5-HT1A receptor. Roxindole also acts as a 5-HT uptake inhibitor with high affinity for 5-HT1A (Ki = 0.9 nM).
|
|---|---|
| ln Vitro |
Roxindole shows >20-fold functional selectivity for D3 over D2 (pEC50 = 9.23 vs 7.88) with low-efficacy D2 partial agonism (Emax = 10.5%). It has affinity for D2-like subtype in low nM range, with IC50 for 5-HT1A of 0.9 nM. It inhibits 5-HT uptake with Ki for SERT around 80 nM.
|
| ln Vivo |
Roxindole hydrochloride suppresses the conditioned avoidance response in rats (ED50=1.5 mg/kg sc) as well as apomorphine-induced climbing in mice and stereotyped behavior in rats (ED50s of 1.4 mg/kg sc and 0.65 mg/kg sc, respectively)[1]. The effects of 8-OH-DPAT (flat body and forepaw treading) in normal rats (male Wistar 200-350g) are inhibited by roxindole hydrochloride (1, 3, 10 mg/kg; sc)[3].
Dopamine D2 autoreceptor agonist that inhibits dopamine release, useful for schizophrenia and depression. In animal models, roxindole shows antipsychotic-like effects without extrapyramidal side effects. It produced rapid-onset antidepressant responses in preclinical models due to combined D3 selectivity and 5-HT1A agonism. It was advanced into clinical trials for schizophrenia. |
| Enzyme Assay |
Cell-free receptor binding assays: Human recombinant dopamine D2, D3, D4 receptors expressed in CHO cells are incubated with [3H]-spiperone (0.5 nM) and increasing concentrations of roxindole (0.01-1000 nM) in 50 mM Tris-HCl, pH 7.4, containing 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 for 60 min at 25degC. Bound radioactivity is separated by filtration. Non-specific binding is determined with 10 uM haloperidol. Ki values are calculated using the Cheng-Prusoff equation. For 5-HT1A receptor binding, [3H]-8-OH-DPAT is used as the radioligand.
|
| Cell Assay |
Functional GTPgammaS assays for D2 and D3 receptors are performed using membranes from CHO cells expressing human receptors. Roxindole (0.01 nM to 10 uM) is incubated with 35S-GTPgammaS (0.1 nM), GDP (10-30 uM), and membrane protein (10-20 ug) in assay buffer for 60 min at 25degC. Bound radioactivity is separated by GF/B filtration. pEC50 values (9.23 for D3, 7.88 for D2) and Emax (% stimulation relative to dopamine) are calculated. For 5-HT uptake inhibition, human serotonin transporter-expressing HEK293 cells are incubated with [3H]-5-HT and roxindole for 10-20 min.
|
| Animal Protocol |
In vivo studies are conducted in male Sprague-Dawley rats. For microdialysis, roxindole is administered subcutaneously (0.1-1 mg/kg) and extracellular dopamine levels in the nucleus accumbens and striatum are measured. For behavioral studies, the forced swim test (FST) for antidepressant activity: roxindole (1-10 mg/kg, i.p. or s.c.) is administered 30-60 min prior to testing, and immobility time is recorded. For antipsychotic-like effects, amphetamine-induced hyperlocomotion or PCP-induced hyperactivity models are used. Formulation: 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (1 mg/mL).
|
| ADME/Pharmacokinetics |
No specific PK data are reported in supplier literature. Roxindole is orally bioavailable and can cross the blood-brain barrier. It has a molecular weight of 382.9 g/mol (HCl salt). The compound is soluble in DMSO. Standard PK parameters (t1/2, Cmax, AUC, F%) have not been published in the available literature. Based on its chemical class, it likely has moderate half-life (2-6 hours) in rodents.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are reported for roxindole hydrochloride. As a dopamine D2 autoreceptor agonist that was evaluated in clinical trials, roxindole demonstrated acceptable tolerability in human studies. The most common adverse events in clinical trials included nausea, dizziness, and headache. Extrapyramidal symptoms were notably absent due to its autoreceptor selectivity. No hepatotoxicity or nephrotoxicity was reported.
|
| References |
|
| Additional Infomation |
See also: Carbidopa (related).
Other information: Roxindole was originally developed by Merck KGaA as an atypical antipsychotic and antidepressant. It reached Phase 2 clinical trials for schizophrenia but was discontinued. It is now used exclusively as a pharmacological tool for investigating neuropsychiatric pathways involving dopamine D2/D3 autoreceptors and 5-HT1A receptors. The compound is available for research purposes only and is not FDA-approved. It has a CAS number of 108050-82-4. |
| Molecular Formula |
C23H27CLN2O
|
|---|---|
| Molecular Weight |
382.93
|
| Exact Mass |
382.181
|
| CAS # |
108050-82-4
|
| Related CAS # |
Roxindole;112192-04-8
|
| PubChem CID |
9886286
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.725
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
27
|
| Complexity |
471
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CN(CC=C1C2=CC=CC=C2)CCCCC3=CNC4=C3C=C(C=C4)O.Cl
|
| InChi Key |
ZCEPVNSWLLJECX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H26N2O.ClH/c26-21-9-10-23-22(16-21)20(17-24-23)8-4-5-13-25-14-11-19(12-15-25)18-6-2-1-3-7-18;/h1-3,6-7,9-11,16-17,24,26H,4-5,8,12-15H2;1H
|
| Chemical Name |
3-[4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)butyl]-1H-indol-5-ol;hydrochloride
|
| 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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO: 50 mg/mL (130.57 mM)
H2O: 1 mg/mL (2.61 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6114 mL | 13.0572 mL | 26.1144 mL | |
| 5 mM | 0.5223 mL | 2.6114 mL | 5.2229 mL | |
| 10 mM | 0.2611 mL | 1.3057 mL | 2.6114 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
