| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
5-HT4 Receptor 18 nM (EC50) T3.36A-5-HT4 77 nM (EC50) W6.48A-5-HT4 540 nM (EC50)
BIMU 8 targets serotonin 5-HT4 and 5-HT3 receptors. It is a potent and selective 5-HT4 receptor agonist with EC50 values of 18 nM for wild-type 5-HT4 receptor. It also binds to 5-HT3 receptors with a Ki of 0.36 nM. The compound displays equal or higher affinity for 5-HT3 receptors as compared to 5-HT4 receptors. It also has affinity for sigma-2 receptors. By activating 5-HT4 receptors and blocking 5-HT3 receptors, the compound modulates gastrointestinal motility and neurotransmitter release. |
|---|---|
| ln Vitro |
BIMU 8 (0.003-0.1 µM) enhances the magnitude of excitatory postsynaptic potentials (EPSPs) in the myenteric neurons of the guinea pig ileum, but it has no effect on any neuron's membrane potential[3].
In vitro, BIMU 8 acts as a potent 5-HT4 receptor agonist. Its activity is typically assessed by measuring its ability to stimulate cAMP accumulation in cells expressing 5-HT4 receptors. The compound shows EC50 values of 18 nM for wild-type 5-HT4 receptor, 77 nM for T3.36A, and 540 nM for W6.48A mutant 5-HT4 receptors. It also shows binding to 5-HT3 receptors with a Ki of 0.36 nM. The EPSP potentiation induced by BIMU 8 was blocked by tropisetron (1 µM), a 5-HT3/5-HT4 receptor antagonist, but not by ondansetron (1 µM), a 5-HT3 receptor antagonist. |
| ln Vivo |
BIMU 8 (20–30 mg/kg sc and 60 mg/kg po in mice; 20 mg/kg ip in rats) significantly reduces pain in mice and rats. A BIMU 8 (10 μg/mouse) intracerebroventricular injection causes an antinociception in mice that is comparable in strength to that of available sc, ip, or po[1]. These doses are essentially useless when administered parenterally.
In vivo, BIMU 8 has been studied in animal models for its effects on gastrointestinal motility and neurotransmitter release. As a 5-HT4 receptor agonist and 5-HT3 receptor antagonist, it would be expected to enhance gastrointestinal motility and modulate serotonergic signaling. In the hot-plate test, the compound's effects have been evaluated. However, comprehensive in vivo efficacy data from published literature are limited. The compound is primarily used as a research tool. |
| Enzyme Assay |
For non-cell-based receptor binding assays, BIMU 8 can be evaluated using membrane preparations from cells expressing human 5-HT4 or 5-HT3 receptors. Radioligand binding displacement experiments are performed using suitable radiolabeled ligands such as [3H]-GR113808 for 5-HT4 or [3H]-GR65630 for 5-HT3. Membrane homogenates are incubated with increasing concentrations of the test compound and a fixed concentration of the radioligand at room temperature for 60-90 minutes. Bound radioligand is separated from free by rapid filtration through glass fiber filters. Non-specific binding is determined in the presence of excess unlabeled ligand. Ki values are calculated from displacement curves using nonlinear regression analysis.
|
| Cell Assay |
For in vitro cellular assays, cells expressing human 5-HT4 or 5-HT3 receptors are cultured in appropriate media. For 5-HT4 agonist assays, cAMP accumulation is measured. Cells are treated with various concentrations of BIMU 8, and cAMP levels are measured using ELISA or HTRF-based detection. EC50 values are calculated from dose-response curves. For 5-HT3 antagonist assays, calcium influx is measured using fluorescent calcium indicators. Cells are loaded with the dye and pre-incubated with various concentrations of the compound. Receptor activation is stimulated by the addition of a 5-HT3 receptor agonist. IC50 values are calculated from dose-response curves.
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| Animal Protocol |
For in vivo animal studies, BIMU 8 can be administered to rodents via intraperitoneal injection. In models of gastrointestinal motility, gastric emptying and intestinal transit are assessed following compound administration. In pain models, the hot-plate test may be used to evaluate analgesic effects. In models of neurotransmitter release, the compound's effects on synaptic transmission are assessed. Dosing regimens vary depending on the specific model and desired exposure levels.
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| ADME/Pharmacokinetics |
BIMU 8 has a molecular weight of 378.90 and a molecular formula of C19H27ClN4O2. It is a potent and selective 5-HT4 receptor agonist. The compound is supplied as a research-grade compound. It should be stored at -20°C for long-term stability. It is soluble in DMSO and can be formulated for both in vitro and in vivo administration. It is for research use only and is not intended for human consumption.
|
| Toxicity/Toxicokinetics |
The toxicity profile of BIMU 8 has not been extensively reported. As a 5-HT4 receptor agonist and 5-HT3 receptor antagonist, potential adverse effects may include modulation of gastrointestinal motility and serotonergic signaling. The compound is for research use only and is not intended for human consumption. Standard toxicological evaluation would include acute and repeated-dose toxicity studies.
|
| References |
[1]. C Ghelardini, et al. Central cholinergic antinociception induced by 5HT4 agonists: BIMU 1 and BIMU 8. Life Sci. 1996;58(25):2297-309.
[2]. Lucie P Pellissier, et al. Conformational toggle switches implicated in basal constitutive and agonist-induced activated states of 5-hydroxytryptamine-4 receptors. Mol Pharmacol. 2009 Apr;75(4):982-90. [3]. H Pan , et al. 5-HT1A and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic transmission in enteric neurons. Am J Physiol. 1994 Feb;266(2 Pt 1):G230-8. |
| Additional Infomation |
BIMU 8 (CAS 134296-40-5) is a potent and selective 5-HT4 receptor agonist with EC50 values of 18 nM, 77 nM, and 540 nM for wild-type 5-HT4 receptor, T3.36A, and W6.48A mutant 5-HT4 receptors, respectively. It has 5-HT4 receptor agonistic and 5-HT3 receptor antagonistic properties. It also binds to 5-HT3 receptors with a Ki of 0.36 nM. It is available for research purposes only.
|
| Molecular Formula |
C19H26CLN4O2-
|
|---|---|
| Molecular Weight |
377.89
|
| Exact Mass |
378.182
|
| CAS # |
134296-40-5
|
| PubChem CID |
5311028
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.511
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
26
|
| Complexity |
538
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
Cl[H].O=C(N1C(N(C([H])(C([H])([H])[H])C([H])([H])[H])C2=C([H])C([H])=C([H])C([H])=C12)=O)N([H])C1([H])C([H])([H])[C@]2([H])C([H])([H])C([H])([H])[C@]([H])(C1([H])[H])N2C([H])([H])[H]
|
| InChi Key |
NQYXXIUVFVOJCX-XZPOUAKSSA-N
|
| InChi Code |
InChI=1S/C19H26N4O2.ClH/c1-12(2)22-16-6-4-5-7-17(16)23(19(22)25)18(24)20-13-10-14-8-9-15(11-13)21(14)3;/h4-7,12-15H,8-11H2,1-3H3,(H,20,24);1H/t13?,14-,15+;
|
| Chemical Name |
N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-3-propan-2-ylbenzimidazole-1-carboxamide;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: 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)
|
| 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
|
|---|---|
| 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 | 2.6463 mL | 13.2314 mL | 26.4627 mL | |
| 5 mM | 0.5293 mL | 2.6463 mL | 5.2925 mL | |
| 10 mM | 0.2646 mL | 1.3231 mL | 2.6463 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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