| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Bifeprunox acts as a partial agonist at dopamine D2 receptors (pKi = 8.83 at striatal D2) and serotonin 5-HT1A receptors (pKi = 7.19 at cortical 5-HT1A; pEC50 = 6.37 at hippocampal 5-HT1A). It also shows affinity for D3 receptors and displays functional selectivity, activating G protein-mediated signaling while antagonizing β-arrestin recruitment. The compound exhibits Emax of approximately 70% at human 5-HT1A receptors relative to full agonists, confirming its partial agonist profile.
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| ln Vitro |
Bifeprunox binds to the h5-HT1A receptor with a pKi of 8 and an Emax of 70% [1].
Bifeprunox has a pKi of 8.0 at human 5-HT1A receptors with an Emax of 70%. At striatal D2 receptors, the pKi is 8.83. The compound demonstrates partial agonist activity at hD2L receptors in [³⁵S]GTPγS binding assays, with intrinsic activity ranging from 20–40% relative to dopamine. In functional assays, bifeprunox activates G protein-coupled inwardly rectifying potassium (GIRK) channels in CHO cells expressing hD2L receptors with an EC50 in the low nanomolar range. |
| ln Vivo |
In mice, marble burying is decreased by bifeprunox (0.001-2.5 mg/kg) [2]. Rats' responses to drug-related cues alter their behavior when they seek nicotine when exposed to bifeprunox (4–250 μg/kg) [3].
In vivo, bifeprunox reduces marble burying in mice (NMRI strain, 20–22 g) at doses of 0.0025–2.5 mg/kg (IP), with significant activity observed from 0.0025 mg/kg. In rats, bifeprunox (4–250 µg/kg, SC) dose-dependently attenuates nicotine-seeking behavior induced by drug-associated cues, with 4–16 µg/kg producing selective effects and higher doses (64–250 µg/kg) reducing spontaneous locomotor activity and operant responding. The compound also suppresses VTA dopaminergic neuron firing via D2 autoreceptor activation and shows anxiolytic-like effects in rodent models. |
| Enzyme Assay |
Radioligand binding assay: Incubate membranes from CHO cells expressing human D2 or 5-HT1A receptors (10–20 µg protein) with [³H]spiperone (D2) or [³H]8-OH-DPAT (5-HT1A) and increasing concentrations of bifeprunox (10⁻¹¹ to 10⁻⁵ M) in assay buffer (50 mM Tris-HCl, pH 7.4, 120 mM NaCl, 5 mM KCl, 2 mM CaCl₂, 1 mM MgCl₂) for 60 minutes at 25°C. Terminate by rapid filtration over GF/B filters, wash, and measure radioactivity by liquid scintillation counting. Determine IC50 and Ki values by non-linear regression. GTPγS binding assay: Incubate membranes with 0.1 nM [³⁵S]GTPγS, 10 µM GDP, and increasing concentrations of bifeprunox for 60 minutes at 30°C. Measure bound radioactivity by filtration.
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| Cell Assay |
Functional assays: Measure GIRK channel activation in CHO cells expressing hD2L and GIRK1/2 subunits by patch-clamp electrophysiology. Determine EC50 and Emax relative to dopamine (100 µM). Assess β-arrestin recruitment using enzyme complementation or BRET assays. For prolactin release, incubate dispersed rat pituitary cells with bifeprunox (10⁻¹⁰ to 10⁻⁵ M) for 4 hours, then measure prolactin in the medium by radioimmunoassay.
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| Animal Protocol |
Animal/Disease Models: Male NMRI mice (body weight 20-22 g) [2]
Doses: 0.001, 0.0025, 0.01, 0.04, 0.16, 0.63 and 2.5 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: diminished marble burial. Effective activity begins at 0.0025 mg/kg. Animal/Disease Models: Naive male Wistar rats (body weight 250-275 g) [3] Doses: 4, 16, 64 and 250 μg/kg Route of Administration: subcutaneous injection 30 minutes before test Experimental Results: 4-16 μg/kg dose dependent Effects of nicotine-related cues on sexually attenuated response restoration. Higher doses (64-250 μg/kg, subcutaneously (sc) (sc)) reduce spontaneous locomotor activity and inhibit operant responses induced by sucrose-related cues and the primary reinforcing properties of nicotine or sucrose. In vivo: Male NMRI mice (20–22 g) or male Wistar rats (250–275 g) are used. Bifeprunox is dissolved in saline and administered IP or SC. For marble burying, place mice individually in cages with 20 glass marbles on bedding for 30 minutes, and count buried marbles. For nicotine-seeking, rats are trained to self-administer nicotine, then tested for cue-induced reinstatement after bifeprunox administration. For electrophysiology, anesthetize rats, perform stereotaxic surgery to implant electrodes in the VTA, and record single-unit activity in response to cumulative bifeprunox doses (1–100 µg/kg, IV). |
| References |
[1]. Newman-Tancredi A, et al. Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia. Int J Neuropsychopharmacol. 2005 Sep;8(3):341-56.
[2]. Bruins Slot LA, et al. Effects of antipsychotics and reference monoaminergic ligands on marble burying behavior in mice. Behav Pharmacol. 2008 Mar;19(2):145-52. [3]. Di Clemente A, et al. Bifeprunox: a partial agonist at dopamine D2 and serotonin 1A receptors, influences nicotine-seeking behaviour in response to drug-associated stimuli in rats. Addict Biol. 2012 Mar;17(2):274-86. |
| Additional Infomation |
Bifilpranol belongs to the biphenyl class of compounds. Bifilpranol is a novel atypical antipsychotic that, like SLV313, [aripiperazole], and SSR-181507, combines minimal D2 receptor agonist activity with 5-HT receptor agonist activity. See also: Bifilpranol mesylate (note moved here). Drug Indications Bifilpranol is being evaluated for the treatment of schizophrenia, psychosis, and Parkinson's disease. Mechanism of Action In contrast to D2 receptor antagonism, partial D2 receptor agonism is thought to reduce dopamine activity in an overactive dopamine system while increasing dopamine activity in hypoactive regions of the brain. By blocking overstimulated receptors and stimulating underactive receptors, partial D2 receptor agonists act as dopamine stabilizers. Similar to aripiprazole, bifilpranol is also a 5-HT1A receptor agonist. This characteristic may help alleviate the negative symptoms of schizophrenia and reduce the incidence of extrapyramidal symptoms (EPS).
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| Molecular Formula |
C24H23N3O2
|
|---|---|
| Molecular Weight |
385.45832
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| Exact Mass |
385.179
|
| CAS # |
350992-10-8
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| Related CAS # |
Bifeprunox mesylate;350992-13-1
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| PubChem CID |
208951
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.247g/cm3
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| Index of Refraction |
1.643
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| LogP |
4.113
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| tPSA |
52.48
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
29
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| Complexity |
556
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC=C(C=C1)C2=CC=CC(=C2)CN3CCN(CC3)C4=CC=CC5=C4OC(=N5)O
|
| InChi Key |
CYGODHVAJQTCBG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H23N3O2/c28-24-25-21-10-5-11-22(23(21)29-24)27-14-12-26(13-15-27)17-18-6-4-9-20(16-18)19-7-2-1-3-8-19/h1-11,16H,12-15,17H2,(H,25,28)
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| Chemical Name |
7-[4-[(3-phenylphenyl)methyl]piperazin-1-yl]-3H-1,3-benzoxazol-2-one
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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 | 2.5943 mL | 12.9715 mL | 25.9430 mL | |
| 5 mM | 0.5189 mL | 2.5943 mL | 5.1886 mL | |
| 10 mM | 0.2594 mL | 1.2972 mL | 2.5943 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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