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| 25mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Diclofensine HCl targets the dopamine transporter (DAT), noradrenaline transporter (NAT), and serotonin transporter (SERT). IC50 values for inhibition of uptake into rat brain synaptosomes: DA = 0.74 nM, NA = 2.3 nM, 5-HT = 3.7 nM [1].
Diclofensine targets the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). It blocks the reuptake of dopamine, noradrenaline, and serotonin by rat brain synaptosomes with IC50 values of 0.74 µM (dopamine), 2.2 µM (noradrenaline), and 3.4 µM (serotonin). |
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| ln Vitro |
Diclofensine HCl potently inhibited the synaptosomal uptake of [3H]dopamine (DA), [3H]noradrenaline (NA), and [3H]serotonin (5-HT) in rat brain. IC50 values were 0.74 nM for DA (striatal synaptosomes), 2.3 nM for NA (frontotemporal cortex synaptosomes), and 3.7 nM for 5-HT (whole brain minus cerebellum, pons, and medulla oblongata synaptosomes) [1].
In receptor binding assays, Diclofensine showed weak or no affinity for dopamine D-2 receptors, α1-adrenoceptors, α2-adrenoceptors, histamine receptors, and 5-HT2 receptors. IC50 values (μM) were: >13,000 for α1, >13,000 for α2, 10,000 for histamine, 11,000 for 5-HT2, and 6,500 for muscarinic receptors (acetylcholine) in isolated organ studies [1]. Diclofensine is a potent inhibitor of monoamine reuptake, blocking the uptake of dopamine, noradrenaline, and serotonin by rat brain synaptosomes with IC50 values of 0.74 µM, 2.2 µM, and 3.4 µM, respectively. It has equipotent inhibitive effects on the neuronal uptake of norepinephrine, serotonin, and dopamine. The compound has been studied as an antidepressant. |
| ln Vivo |
Diclofensine HCl had an effect only in the 6-hydroxydopamine (6-OHDA) circling model in unilaterally lesioned rats, but no specific in vivo data on depletion reversal were presented in this paper. In the 6-OHDA-induced depletion model in mouse brain, no quantitative data were provided for diclofensine [1].
In vivo, Diclofensine has been studied for its potential use in the treatment of various neurological and psychiatric disorders, including depression. By inhibiting the reuptake of all three monoamines, it increases synaptic levels of dopamine, noradrenaline, and serotonin, which are implicated in mood regulation. |
| Enzyme Assay |
Cell-free assays for Diclofensine utilize membrane preparations from rat brain synaptosomes expressing DAT, NET, and SERT. [3H]-dopamine, [3H]-noradrenaline, or [3H]-serotonin uptake is measured in the presence of increasing concentrations of the compound. Inhibition of uptake is quantified, and IC50 values are determined from concentration-response curves.
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| Cell Assay |
Synaptosomal uptake inhibition assay: Rat brain synaptosomes were prepared from corpus striatum (DA), frontotemporal cortex (NA), or whole brain minus cerebellum, pons, and medulla oblongata (5-HT). Synaptosomes were incubated with [3H]amine (final concentration: 10 nM for DA, 10 nM for NA, 10 nM for 5-HT) and various concentrations of Diclofensine for 30 min at 37°C, then filtered. Unspecific binding was determined in the presence of 100 μM benzotriene (DA), 10 μM citalopram (5-HT), or 10 μM talsupram (NA). IC50 values were calculated from concentration-response curves [1].
Receptor binding assays: Tissues were homogenized and centrifuged. For D-2, α1, 5-HT2, and muscarinic binding, specific radioligands ([3H]spiroperidol, [3H]prazosin, [3H]spiroperidol with sulpiride, [3H]PrBCM) were used. Incubation conditions varied (see Table 1). Bound radioactivity was measured by filtration. Diclofensine was tested at multiple concentrations [1]. Functional organ assays: Isolated guinea pig ileum (muscarinic, histaminergic, α2-adrenergic), rabbit pulmonary artery (α1-adrenergic), and rat fundus (5-HT2) were used to measure antagonist activity against agonist-induced contractions. IC50 values were determined [1]. Cells expressing DAT, NET, or SERT (e.g., HEK293 cells transfected with the transporters) are incubated with radiolabeled monoamines ([3H]-dopamine, [3H]-noradrenaline, [3H]-serotonin) in the presence of Diclofensine at various concentrations. Uptake is quantified by scintillation counting. IC50 values are determined from concentration-response curves. Selectivity for each transporter is assessed. |
| Animal Protocol |
In vivo animal studies for Diclofensine are conducted in rodent models of depression and other neuropsychiatric disorders. The compound is administered via intraperitoneal or oral routes. Behavioral assays (e.g., forced swim test, tail suspension test) are performed to assess antidepressant-like effects. Monoamine levels in brain tissue are measured by HPLC or microdialysis.
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| ADME/Pharmacokinetics |
Diclofensine is orally bioavailable. As a small molecule (MW 358.69, formula C17H18Cl3NO) with moderate lipophilicity, it has favorable drug-like properties for CNS penetration. PK parameters including Tmax, half-life, clearance, and bioavailability have been characterized in preclinical species.
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| Toxicity/Toxicokinetics |
Toxicity data for Diclofensine are limited. As a triple monoamine reuptake inhibitor, it has potential for cardiovascular effects (hypertension, tachycardia) similar to other monoamine reuptake inhibitors. Standard toxicological assessments including genotoxicity, reproductive toxicity, and chronic toxicity studies would be required for development.
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| References | |
| Additional Infomation |
Diclofensine HCl (Ro 8-4650) is a potent and equipotent inhibitor of DA, NA, and 5-HT uptake. It was developed by Hoffmann‑La Roche. In this study, it was used as a comparator to the novel compound Lu 19-005. Diclofensine showed weak receptor binding affinities, indicating selectivity for monoamine transporters over neurotransmitter receptors. Its profile resembles that of Lu 19-005 but with slightly lower potency [1].
Diclofensine HCl (molecular formula C17H18Cl3NO, MW 358.69) is also known as Ro-8-4650 hydrochloride. It is a tetrahydroisoquinoline-based triple monoamine reuptake inhibitor that was studied as an antidepressant. The compound is a racemic mixture whose (S)-enantiomer is primarily responsible for its biological activity. It is intended for research use only. |
| Molecular Formula |
C17H17NOCL2.HCL
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|---|---|
| Molecular Weight |
358.68992
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| Exact Mass |
357.045
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| CAS # |
34041-84-4
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| Related CAS # |
Diclofensine;67165-56-4
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| PubChem CID |
157489
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| Appearance |
White to off-white solid powder
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| LogP |
5.319
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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| Complexity |
354
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CC2=C(C=CC(OC)=C2)C(C3=CC=C(Cl)C(Cl)=C3)C1.[H]Cl
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| InChi Key |
PEHOXCSPLOXNOK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H17Cl2NO.ClH/c1-20-9-12-7-13(21-2)4-5-14(12)15(10-20)11-3-6-16(18)17(19)8-11;/h3-8,15H,9-10H2,1-2H3;1H
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| Chemical Name |
4-(3,4-dichlorophenyl)-7-methoxy-2-methyl-3,4-dihydro-1H-isoquinoline;hydrochloride
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| Synonyms |
Diclofensine hydrochloride; 34041-84-4; Ro-84650; 8U71XY6JQK; RO-8-4650;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, 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)
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| Solubility (In Vitro) |
H2O : ≥ 52 mg/mL (~144.97 mM)
DMSO : ~6.67 mg/mL (~18.60 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.67 mg/mL (1.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 6.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7879 mL | 13.9396 mL | 27.8792 mL | |
| 5 mM | 0.5576 mL | 2.7879 mL | 5.5758 mL | |
| 10 mM | 0.2788 mL | 1.3940 mL | 2.7879 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.
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