| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
DOV-102,677 is a “triple” monoamine reuptake inhibitor that simultaneously targets the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). The functional inhibition IC50 values for the three transporters are: DAT 129 nM, NET 103 nM, and SERT 133 nM. The binding affinities (Ki values) are: DAT 222 nM, NET 1030 nM, and SERT 740 nM. These data indicate that the compound exhibits relatively balanced inhibition across all three transporters.
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| ln Vitro |
DOV-102,677 was characterized in vitro using radioligand binding and neurotransmitter uptake assays. In HEK-293 cells expressing human recombinant transporters, the compound inhibited [³H]dopamine, [³H]norepinephrine, and [³H]serotonin uptake with IC50 values of 129 nM, 103 nM, and 133 nM, respectively. Competitive binding assays using the radioligand [125I]RTI-55 gave Ki values of 222 nM for DAT, 1030 nM for NET, and 740 nM for SERT. [
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| ln Vivo |
Neurochemical effects: Using in vivo microdialysis in rats, DOV-102,677 (20 mg/kg, i.p.) increased extracellular levels of DA and 5-HT in the prefrontal cortex to 320% and 280% of baseline, respectively, at 100 minutes post-administration. The elevation of DA remained stable throughout the 240-minute study, while 5-HT levels returned to baseline after 200 minutes. NE levels increased linearly to a maximum of 348% at 240 minutes. Long-term oral administration (20 mg/kg/day for 35 days) selectively decreased β-adrenergic receptor density in the rat cortex.
Antidepressant-like activity: In the forced swim test, DOV-102,677 dose-dependently reduced immobility time in rats (MED = 20 mg/kg), with maximal efficacy comparable to imipramine. This reduction was not due to increased locomotor activity. Anti-alcohol effects: In alcohol-preferring rats, DOV-102,677 (6.25-50 mg/kg, p.o.) dose-dependently reduced alcohol-maintained responding by 59-88% at 25 minutes post-dose without affecting sucrose responding. The effect persisted for 24 hours after a single dose, with the 50 mg/kg dose inhibiting alcohol responding by 44-62% over 48 hours. |
| Enzyme Assay |
Radioligand competition binding assays were performed using HEK-293 cells stably expressing human recombinant DAT, NET, or SERT. Cells were grown to confluence in medium supplemented with serum and antibiotics. [125I]RTI-55 was used as the radioligand. Cell suspension aliquots (50 μL) were added to tubes containing various concentrations of DOV-102,677 and Krebs-HEPES assay buffer (final volume 0.5 mL). After incubation in a 25°C water bath, the reaction was terminated by vacuum filtration, and radioactivity on the filters was measured using a gamma counter or imaging system. Specific binding was defined as the difference between binding in the absence and presence of an excess of competitor (e.g., 5 μM mazindol for DAT/NET, 5 μM imipramine for SERT). Ki values were calculated by nonlinear regression analysis.
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| Cell Assay |
Neurotransmitter uptake inhibition assays were performed using the same HEK-293 cell lines expressing human recombinant DAT, NET, or SERT. After a 10-minute preincubation at 25°C, radiolabeled substrates ([³H]DA, [³H]NE, or [³H]5-HT at a final concentration of 20 nM) were added, and incubation continued for 10 minutes. The reaction was terminated by vacuum filtration onto Whatman GF/C filters using a Tomtec cell harvester. Filters were soaked in scintillation fluid, and radioactivity was measured by liquid scintillation counting. Percent inhibition at each compound concentration was calculated, and IC50 values were derived by nonlinear regression analysis of concentration-inhibition curves.
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| Animal Protocol |
Rat In Vivo Microdialysis: Rats were anesthetized, and guide cannulae were stereotaxically implanted into the prefrontal cortex. After recovery, microdialysis probes were inserted and perfused with artificial cerebrospinal fluid at a constant flow rate (e.g., 1.5 μL/min). Baseline samples were collected, followed by intraperitoneal administration of DOV-102,677 (20 mg/kg). Dialysate samples were collected for up to 240 minutes. Monoamine and metabolite concentrations were analyzed by HPLC with electrochemical detection.
Forced Swim Test: Rats were pretested with a 15-minute swim. Twenty-four hours later, DOV-102,677 (12.5-50 mg/kg, p.o.) or vehicle was administered. At 25 minutes post-dose, rats were placed in the swim apparatus, and immobility time was recorded during a 6-minute test session. Alcohol Self-Administration: Alcohol-preferring rats were trained to respond on a lever under an FR4 schedule for 10% alcohol or sucrose solution. DOV-102,677 (1.56-50 mg/kg, p.o.) was administered 25 minutes or 24 hours before the test session. Total responses for alcohol or sucrose were measured over 20-40 minutes. |
| ADME/Pharmacokinetics |
DOV-102,677 is rapidly absorbed after oral administration with good bioavailability. In rats, 20 mg/kg/day oral administration for 35 days produced sufficient exposure to induce neurochemical changes such as decreased β-adrenergic receptor density. The compound has a long duration of action: in alcohol-preferring rats, inhibition of alcohol-seeking behavior was still detectable 24 hours after a single oral dose (44% inhibition at 50 mg/kg), suggesting a long elimination half-life or the presence of an active metabolite. Physicochemical properties: molecular weight 228.12 g/mol, CLogP 3.
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| Toxicity/Toxicokinetics |
In preclinical studies, DOV-102,677 was generally well-tolerated. At doses up to 50 mg/kg (p.o.), no significant increase in locomotor activity was observed post-administration (indicating absence of psychostimulant-like side effects), and sucrose self-administration behavior was not altered, suggesting behavioral selectivity. The antidepressant-like effects in the forced swim test were independent of changes in motor function. However, Phase I clinical trials for depression were discontinued in the United States, though specific toxicity data are not detailed in the available literature. The compound is currently being investigated for the treatment of alcohol use disorder. As a psychotropic agent, it should be handled with caution and used only under professional guidance.
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| References | |
| Additional Infomation |
DOV-102,677 (CAS: 410074-75-8) has the molecular formula C₁₁H₁₁Cl₂N and a molecular weight of 228.12 g/mol. The IUPAC name is (1S,5R)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane. This compound is the single enantiomer of Amitifadine (the (−)-enantiomer). DOV-102,677 was initially discovered by DOV Pharmaceutical and subsequently developed in partnership with Merck & Co. Although Phase I clinical trials for depression have been discontinued, the compound has shown promise in preclinical models of alcohol use disorder and is currently being advanced in that direction. Its discovery was based on the hypothesis that “balanced” triple reuptake inhibitors might be more effective for treating depression and comorbid conditions. DOV-102,677 represents an important research direction extending the classical monoamine hypothesis toward more comprehensive modulation of mood-related neurotransmitter systems. This product is for research use only and is not for human therapeutic use.
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| Molecular Formula |
C11H11CL2N
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|---|---|
| Molecular Weight |
228.117740869522
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| Exact Mass |
227.0269
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| Elemental Analysis |
C, 57.92; H, 4.86; Cl, 31.08; N, 6.14
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| CAS # |
410074-75-8
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| Related CAS # |
410074-74-7; 410074-73-6; 410074-75-8; 66504-40-3
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| PubChem CID |
11637190
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
14
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| Complexity |
245
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| Defined Atom Stereocenter Count |
2
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| SMILES |
[C@@]12(C3=CC=C(Cl)C(Cl)=C3)[C@@]([H])(C1)CNC2
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| InChi Key |
BSMNRYCSBFHEMQ-GZMMTYOYSA-N
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| InChi Code |
InChI=1S/C11H11Cl2N/c12-9-2-1-7(3-10(9)13)11-4-8(11)5-14-6-11/h1-3,8,14H,4-6H2/t8-,11+/m0/s1
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| Chemical Name |
(1S,5R)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane
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| Synonyms |
NS8NWQ6NF4; UNII-NS8NWQ6NF4; DOV 102677; DOV102677; DOV102,677; DOV 102,677; DOV-102677; DOV-102,677
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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 |
| 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) |
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
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| 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 | 4.3837 mL | 21.9183 mL | 43.8366 mL | |
| 5 mM | 0.8767 mL | 4.3837 mL | 8.7673 mL | |
| 10 mM | 0.4384 mL | 2.1918 mL | 4.3837 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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