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Purity: ≥98%
BD-1063 HCl (BD1063 hydrochloride) is a novel, potent and selective sigma receptor antagonist with the potential for treating alcoholism. It exhibits a Ki of 9 ± 1 nM for the sigma-1 receptor and shows more than 49 times selectivity over the sigma-2 receptor. Consistent with other reported sigma receptor antagonists, pretreating Swiss Webster mice with BD1063 significantly decreases the convulsivity and lethality of cocaine. In other animal studies, BD1063 blocks the effects of MDMA, and reduces alcohol intake in rodent models of alcoholism.
| Targets |
Sigma-1 receptor (Sig-1R) antagonist. BD-1063 has preferential, nanomolar affinity for Sig-1Rs and is 30-fold selective for Sig-1R versus Sig-2R sites.[1]
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| ln Vitro |
The study does not contain classic in vitro pharmacological activity assays (e.g., anti-proliferation, enzyme inhibition). The primary in vitro component is quantitative PCR analysis of gene expression.[1]
Quantitative real-time PCR showed that Sig-1R mRNA levels were significantly lower in the nucleus accumbens of ethanol-naïve Sardinian alcohol-preferring (sP) rats and 24-hr withdrawn, ethanol-dependent Wistar rats, compared to ethanol-naïve outbred Wistar controls. No significant differences were observed in the ventral tegmental area, central amygdala, or basolateral amygdala.[1] |
| ln Vivo |
At dosages that do not alter the mean ethanol self-administration in non-dependent Wistar controls, BD1063 dose-dependently decreases the amount of ethanol self-administration in sP rats (3.3-11 mg/kg) and withdrawn, dependent Wistar rats (4-11 mg/kg). Additionally, BD1063 lowers the breakpoints for sP rats to labor for ethanol in a reinforcement schedule with a progressive ratio[1]. In Palatable rats, BD1063 inhibits the elevated eating rate and decreases binge-like eating as well as the regularity of food response in a dose-dependent manner. Without influencing motor activity, BD1063 opposes both the increased consumption of the palatable food and the longer time spent in the unpleasant compartment in the light/dark conflict test[2]. In WT mice, BD1063 is administered half an hour prior to each paclitaxel treatment, preventing the development of mechanical and cold allodynia. Furthermore, both forms of paclitaxel-induced allodynia are reversed by the acute dose-dependent injection of BD1063[3].
ubcutaneous administration of BD-1063 dose-dependently reduced operant oral ethanol self-administration in two animal models of excessive drinking: 1) acutely withdrawn, ethanol-dependent Wistar rats (4-11 mg/kg), and 2) genetically selected Sardinian alcohol-preferring (sP) rats (3.3-11 mg/kg). Doses up to 11 mg/kg did not significantly modify mean ethanol self-administration in non-dependent Wistar control rats.[1] BD-1063 (4.4-11 mg/kg) reduced the breakpoint for ethanol under a progressive-ratio reinforcement schedule in sP rats, indicating a reduction in the motivation to work for ethanol.[1] The effects were selective for ethanol reinforcement. BD-1063 did not reduce concurrent water self-administration, nor did it comparably suppress self-administration of an equally reinforcing saccharin solution in Wistar or sP rats.[1] The highest dose tested (11 mg/kg, s.c.) decreased fixed-ratio operant responding for ethanol by 37% in dependent Wistar rats and 42% in sP rats.[1] |
| Enzyme Assay |
BD-1063. The primary biochemical characterization is a radioligand receptor binding assay, detailed below.[3]
Radioligand Binding Assay for Sigma-1 Receptor Affinity and Competition: Crude synaptosomal membranes (P2 fraction) were prepared from whole mouse brains. Membrane aliquots were thawed and resuspended in incubation buffer (50 mM Tris-HCl, pH 8.0). For competition assays, membranes were incubated at 30°C for 240 minutes with a fixed concentration (5 nM) of the σ1 receptor radioligand [³H](+)-pentazocine and increasing concentrations (10⁻¹⁰ to 10⁻⁵ M) of unlabeled BD-1063 or its solvent. Non-specific binding was defined in the presence of 10 μM haloperidol. The reaction was terminated by adding ice-cold filtration buffer, and bound radioactivity was separated by rapid vacuum filtration through glass fiber filters pre-soaked in polyethylenimine. Filter-bound radioactivity was quantified by liquid scintillation counting. IC50 and Ki values were determined from the inhibition curves.[3] Saturation Binding Assay for Competitive Interaction: Saturation binding isotherms for [³H](+)-pentazocine (0.06–33 nM) were generated in the absence and presence of a fixed, near-IC50 concentration of unlabeled BD-1063 (12.5 nM). Membranes were incubated as above. KD and Bmax values were determined by nonlinear regression analysis of saturation curves. A significant increase in KD without a change in Bmax in the presence of BD-1063 indicated competitive antagonism.[3] |
| Animal Protocol |
Rats: BD-1063 HCl (BD1063 hydrochloride) is solubilized in isotonic saline and injected subcutaneously (s.c. 1 ml/kg), 15 min before testing. Rats are pretreated with BD1063 (0, 4.4, 7 and 11 mg/kg of body weight, free base weights, s.c.) using a within-subject Latin square design. sP rats: Rats are pretreated with BD1063 (0, 3, 4.4, 7 and 11 mg/kg of body weight, free base basis, s.c.) using a within-subject Latin square design[1].
Ethanol Self-Administration in Rats: Male Wistar and Sardinian alcohol-preferring (sP) rats were used. For operant training, rats pressed a lever on a fixed-ratio 1 schedule to receive 0.1 ml of 10% (v/v) ethanol solution during daily sessions (30-min for Wistar, 60-min for sP). Drug Treatment: BD-1063 was solubilized in isotonic saline and administered subcutaneously at a volume of 1 mL/kg, 15 minutes before the behavioral testing session. Doses tested were based on the free base weight: 0, 4.4, 7, 11 mg/kg for Wistar rats; 0, 3, 4.4, 7, 11 mg/kg for sP rats. A within-subject Latin square design was used.[1] Ethanol Dependence Model: Wistar rats were made ethanol-dependent via intermittent exposure to ethanol vapor (14 hours on/10 hours off daily for 6 weeks), achieving target blood alcohol levels of 150-200 mg%. Operant testing began 6 hours after vapor offset during acute withdrawal.[1] Progressive-Ratio Schedule: sP rats were trained to self-administer ethanol under a progressive-ratio schedule where the response requirement increased exponentially. The session ended when no response occurred for 15 minutes. Breakpoint was defined as the last ratio completed.[1] Saccharin Control: To assess specificity, separate groups of rats were trained to self-administer a saccharin solution (concentration adjusted to match baseline response rates for ethanol) under an FR1 schedule, followed by BD-1063 pretreatment.[1] |
| Toxicity/Toxicokinetics |
It is worth noting that previous reports have shown that BD-1063 and its related compound BD-1047 at doses up to 30 mg/kg did not exhibit motor inhibition, suggesting that they do not cause generalized behavioral inhibition or acute toxicity at the tested doses. [1]
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| References |
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| Additional Infomation |
1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine is a primary amine. BD-1063 is a potent and selective σ-1 receptor (Sig-1R) antagonist. σ receptors are associated with the behavioral effects of psychostimulants. This study suggests that the Sig-1R system may be associated with excessive ethanol intake and fortification, and is therefore considered a potential target for the treatment of alcohol abuse and dependence. [1] Sig-1R mRNA expression was reduced in the nucleus accumbens of ethanol-naïve sP rats and withdrawal-dependent rats, suggesting a possible neural adaptation mechanism that may be associated with an innate or ethanol-induced increased susceptibility to high ethanol intake. [1] The mechanism by which Sig-1R antagonists reduce the fortification effect of ethanol may involve indirect regulation of dopaminergic transmission in the mesolimbic pathway and/or interference with intracellular calcium signaling associated with the endoplasmic reticulum. [1]
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| Molecular Formula |
C13H18N2CL2.2[HCL]
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| Molecular Weight |
346.1233
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| Exact Mass |
344.038
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| CAS # |
206996-13-6
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| Related CAS # |
Related CAS 206996-13-6 (HCl); 150208-28-9
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| PubChem CID |
574780
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| Appearance |
White to off-white solid powder
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| LogP |
4.263
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
17
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| Complexity |
230
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NXFDBTLQOARIMH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H18Cl2N2.2ClH/c1-16-6-8-17(9-7-16)5-4-11-2-3-12(14)13(15)10-11;;/h2-3,10H,4-9H2,1H3;2*1H
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| Chemical Name |
1-[2-(3,4-dichlorophenyl)ethyl]-4-methyl-piperazine, dihydrochloride
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| Synonyms |
BD1063; BD 1063; BD-1063;
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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 : ~100 mg/mL (~288.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (288.92 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8892 mL | 14.4459 mL | 28.8917 mL | |
| 5 mM | 0.5778 mL | 2.8892 mL | 5.7783 mL | |
| 10 mM | 0.2889 mL | 1.4446 mL | 2.8892 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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