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| Targets |
6-Benzoylheteratisine targets voltage-gated sodium channels, which are critical for the generation and propagation of action potentials in neurons. By blocking sodium channels, the compound inhibits the influx of sodium ions into neurons, thereby reducing neuronal excitability. This mechanism underlies its ability to antagonize tetrodotoxin, a potent sodium channel blocker. The compound also inhibits the increase in intracellular sodium ([Na+]i) and calcium ([Ca2+]i) that occurs upon neuronal stimulation, as well as inhibiting glutamate release. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its excessive release is associated with excitotoxicity and neuronal damage. By inhibiting sodium channel activity and downstream calcium influx and glutamate release, 6-Benzoylheteratisine may exert neuroprotective effects. The compound's ability to inhibit epileptiform activity further supports its action on neuronal excitability.
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| ln Vitro |
In vitro, 6-Benzoylheteratisine has been shown to inhibit stimulus-triggered epileptiform activity recorded in the CA1 stratum pyramidale of hippocampal slices. The compound decreases the amplitude of the presynaptic fiber spike at all stimulus intensities tested and shifts the stimulus-response curve to the right. At a concentration of 3 μM, 6-Benzoylheteratisine effectively reduces neuronal excitability. The compound antagonizes tetrodotoxin and inhibits the increase in intracellular sodium ([Na+]i) and calcium ([Ca2+]i) that occurs upon neuronal stimulation. It also inhibits glutamate release, which is a key mediator of excitotoxicity. These in vitro activities suggest that 6-Benzoylheteratisine has potential as a neuroprotective agent and as a tool for studying sodium channel function and epileptogenesis. However, specific quantitative data such as IC50 values for sodium channel blockade have not been extensively reported.
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| ln Vivo |
In vivo activity of 6-Benzoylheteratisine has not been extensively reported in the available literature. Based on its in vitro effects as a sodium channel blocker and inhibitor of epileptiform activity, the compound would be expected to have anticonvulsant and neuroprotective effects in vivo. However, specific animal model studies, dosing regimens, and quantitative outcomes have not been reported. The compound is an Aconitum alkaloid, and other alkaloids from Aconitum species have been studied for their effects on pain, inflammation, and neurological disorders. However, the in vivo pharmacology of 6-Benzoylheteratisine specifically remains to be characterized. Further in vivo studies would be required to assess its efficacy, safety, and pharmacokinetic properties in animal models of epilepsy, stroke, or other neurological conditions.
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| Enzyme Assay |
In vitro enzyme or receptor binding assay protocols for 6-Benzoylheteratisine would typically involve measuring its effects on sodium channel function using electrophysiological techniques. A standard protocol would involve preparing brain slices (e.g., hippocampal slices) from rodents and recording field potentials or whole-cell patch-clamp recordings from neurons in the CA1 region. The compound is applied to the bath solution at concentrations ranging from 0.1 to 10 μM, and its effects on stimulus-evoked responses, action potential firing, and sodium currents are measured. For sodium channel binding studies, radioligand binding assays using 3H-tetrodotoxin or 3H-saxitoxin as radioligands and membrane preparations from brain tissue can be employed. The compound's ability to displace radiolabeled toxins from sodium channels can be used to calculate IC50 and Ki values. Alternatively, fluorescence-based membrane potential assays using voltage-sensitive dyes can be used for high-throughput screening of sodium channel activity.
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| Cell Assay |
In vitro cell-based assay protocols for 6-Benzoylheteratisine would typically involve assessing its effects on neuronal excitability and glutamate release in cultured neurons. A standard protocol would involve preparing primary neuronal cultures (e.g., from embryonic rat or mouse cortex or hippocampus) and culturing them for 7-14 days. Neurons are treated with varying concentrations of 6-Benzoylheteratisine (typically 0.1 to 10 μM) for a defined period (e.g., 30-60 minutes), and neuronal activity is assessed using calcium imaging with fluorescent calcium indicators such as Fluo-4 or Fura-2. Glutamate release can be measured using enzyme-linked assays or by collecting culture media and analyzing glutamate content by HPLC or biosensor. For studying epileptiform activity, neuronal cultures can be treated with convulsants such as 4-aminopyridine or bicuculline to induce epileptiform activity, and the effects of 6-Benzoylheteratisine on this activity can be assessed. Appropriate controls include vehicle-treated neurons and positive controls such as tetrodotoxin.
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| Animal Protocol |
In vivo animal experimental protocols for 6-Benzoylheteratisine have not been extensively reported. Based on its mechanism as a sodium channel blocker and its in vitro effects on epileptiform activity, potential studies might involve administering the compound to rodents in models of epilepsy or seizure. A hypothetical protocol for studying its anticonvulsant effects would involve administering 6-Benzoylheteratisine (e.g., intraperitoneally or intracerebroventricularly) to mice or rats, followed by induction of seizures using pentylenetetrazole (PTZ) or maximal electroshock (MES). The dose of 6-Benzoylheteratisine would need to be determined from preliminary studies, and the latency to seizure onset, seizure severity, and mortality would be recorded. For neuroprotection studies, the compound could be administered before or after induction of ischemic stroke (e.g., middle cerebral artery occlusion) or traumatic brain injury, and outcomes such as infarct size, neurological score, and neuronal survival would be assessed. However, specific published protocols are not available.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of 6-Benzoylheteratisine have not been characterized in published studies. As an Aconitum alkaloid with a complex structure, the compound would be expected to have moderate lipophilicity and the ability to cross the blood-brain barrier, consistent with its CNS activity. However, specific PK parameters such as half-life, Cmax, AUC, bioavailability, volume of distribution, and clearance have not been reported. The compound's metabolism, protein binding, and routes of elimination remain uncharacterized. Given that it is a natural product alkaloid, it may undergo hepatic metabolism via cytochrome P450 enzymes. Further pharmacokinetic studies would be required to understand its absorption, distribution, metabolism, and excretion profile. The compound should be stored under recommended conditions to maintain stability.
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| Toxicity/Toxicokinetics |
Toxicological data for 6-Benzoylheteratisine are limited, as the compound is intended for research use only and has not undergone systematic toxicity testing. No acute toxicity (LD50), subchronic toxicity, genotoxicity, or reproductive toxicity studies have been reported specifically for this compound. As an Aconitum alkaloid, it may share some toxicological properties with other aconite alkaloids, which are known to be highly toxic due to their effects on sodium channels and the cardiovascular system. Aconitine and related alkaloids can cause cardiac arrhythmias, hypotension, and respiratory depression. However, the specific toxicity profile of 6-Benzoylheteratisine has not been characterized. The compound is not intended for human use. Researchers should exercise extreme caution when handling this compound and follow appropriate safety precautions, including working in a fume hood, wearing appropriate personal protective equipment, and avoiding inhalation, ingestion, or skin contact.
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| References |
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| Additional Infomation |
6-Benzoylheteratisine is a research-grade Aconitum alkaloid that functions as a voltage-gated sodium channel blocker with potential neuroprotective activity. It antagonizes tetrodotoxin, inhibits increases in intracellular sodium and calcium, and inhibits glutamate release. The compound inhibits stimulus-triggered epileptiform activity in hippocampal slices and decreases presynaptic fiber spike amplitude. It has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action involves blockade of voltage-gated sodium channels, reducing neuronal excitability and potentially providing neuroprotection against excitotoxicity. The compound is used in neuropharmacological research to study sodium channel function, epilepsy, and neuroprotection. It is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
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| Molecular Formula |
C29H37NO6
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|---|---|
| Molecular Weight |
495.61
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| Exact Mass |
495.262
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| CAS # |
99759-48-5
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| PubChem CID |
5487064
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| Appearance |
Solid powder
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| Density |
1.32g/cm3
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| Boiling Point |
645.9ºC at 760 mmHg
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| Flash Point |
344.4ºC
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| Index of Refraction |
1.622
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| LogP |
2.987
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
950
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| Defined Atom Stereocenter Count |
6
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| SMILES |
C1C=C(C=CC=1)C(O[C@H]1[C@@]2([H])C34[C@H](CC[C@@]2(C)CN(CC)C3C1[C@@]1([C@]2(C(=O)O[C@](C[C@@]42[H])(CC1)[H])[H])O)OC)=O
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| InChi Key |
XVVZJDDPRFFKTQ-UPWHZOCASA-N
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| InChi Code |
InChI=1S/C29H37NO6/c1-4-30-15-27(2)12-11-19(34-3)29-18-14-17-10-13-28(33,20(18)26(32)35-17)21(24(29)30)22(23(27)29)36-25(31)16-8-6-5-7-9-16/h5-9,17-24,33H,4,10-15H2,1-3H3/t17-,18?,19-,20?,21?,22+,23+,24?,27-,28+,29?/m0/s1
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| Chemical Name |
[(6S,9S,14R,17S,18R,19S)-12-ethyl-9-hydroxy-17-methoxy-14-methyl-4-oxo-5-oxa-12-azahexacyclo[8.7.2.12,6.01,11.03,9.014,18]icosan-19-yl] benzoate
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
Typically soluble in DMSO (e.g. 10 mM)
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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 | 2.0177 mL | 10.0886 mL | 20.1772 mL | |
| 5 mM | 0.4035 mL | 2.0177 mL | 4.0354 mL | |
| 10 mM | 0.2018 mL | 1.0089 mL | 2.0177 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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