| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg | |||
| Other Sizes |
| Targets |
Thioperamide targets histamine H3 receptors and H4 receptors. It acts as a potent H3 receptor antagonist with a Ki of 4.3 nM for inhibition of [³H]histamine release and a Ki of 31 nM for inhibition of [³H]histamine synthesis. For human recombinant H3 and H4 receptors, Ki values are 25 and 27 nM, respectively. By blocking H3 autoreceptors, Thioperamide negatively regulates histamine release and enhances the activity of histaminergic neurons. This mechanism increases histaminergic neurotransmission in the brain.
|
|---|---|
| ln Vitro |
In guinea pig lung and rat brain, thioperamide suppresses [3H]-(R)α-MeHA binding with Kis values of 2.0 nM and 2.1 nM, respectively. With an average apparent Ki of 4 nM, thioperamide competitively inhibits H3 autoreceptors that drive [3H]histamine release [1]. In a concentration-dependent manner, thioperamide (0.01-100 μM; 24 hours) increases the vitality of NE-4C stem cells [2].
Thioperamide demonstrates potent in vitro activity as a histamine H3 receptor antagonist. It inhibits [³H]histamine release with a Ki of 4.3 nM and inhibits [³H]histamine synthesis with a Ki of 31 nM. The compound also acts as an H4 receptor antagonist/inverse agonist with Ki values of 25 nM (H3) and 27 nM (H4) for human recombinant receptors. These in vitro binding data confirm its potent and dual-target activity at histamine receptors. Specific details on assay conditions and comparative data are not extensively provided. |
| ln Vivo |
In C57BL/6J mice, thioperamide (5–20 mg/kg; intraperitoneal injection) can help reconsolidate fear memory that has been contextually conditioned [3].
Thioperamide demonstrates in vivo activity as a brain-permeable H3 receptor antagonist. By blocking H3 autoreceptors, it enhances the activity of histaminergic neurons. This leads to increased histamine release and neurotransmission in the brain. The compound is orally active, making it suitable for oral administration. Specific in vivo efficacy data, including behavioral effects, cognitive enhancement, and wake-promoting effects, are not extensively provided in the available literature. The compound's brain permeability suggests potential for central nervous system applications. |
| Enzyme Assay |
In vitro receptor binding assays for Thioperamide involve measuring affinity for histamine H3 and H4 receptors. Membrane preparations from cells expressing human recombinant H3 or H4 receptors are incubated with radiolabeled ligands (e.g., [³H]N-methylhistamine for H3, [³H]histamine for H4) and varying concentrations of Thioperamide (typically 0.01-1000 nM) at room temperature for 60-120 minutes. Non-specific binding is determined in the presence of excess unlabeled ligand. Bound radioactivity is collected by filtration onto glass fiber filters and quantified by scintillation counting. Ki values are calculated from competition curves.
|
| Cell Assay |
Cell viability assay [2]
Cell Types: NE-4C stem cell Tested Concentrations: 0.01, 0.1, 1, 10, 100 μM Incubation Duration: 24 hrs (hours) Experimental Results: NE-4C stem cell viability Dramatically increased to 150.83±6.91% (administered 1μM), It increased to 145.11±14.52% and 132.02%±25.65% when 10 μM and 100 μM were applied, respectively. For in vitro cell-based assays, cells expressing histamine H3 or H4 receptors are cultured in appropriate medium. Cells are treated with Thioperamide at various concentrations (typically 0.01-1000 nM). Receptor activation is measured by assessing downstream signaling pathways (e.g., cAMP accumulation for H3, calcium mobilization for H4). For histamine release assays, cells or tissue slices are preloaded with [³H]histamine, stimulated with depolarizing agents, and [³H]histamine release is measured in the presence of Thioperamide. Histamine synthesis is assessed by measuring histidine decarboxylase activity or by measuring histamine levels by HPLC. |
| Animal Protocol |
Animal/Disease Models: Naive female C57BL/6J mice [3]
Doses: 5, 10 or 20 mg/kg Route of Administration: injection (ip) Experimental Results: Promote the reconsolidation of contextually conditioned fear memory. In vivo animal studies for Thioperamide typically use rodent models to assess H3 receptor antagonism. The compound is administered orally or intraperitoneally at doses determined from pharmacokinetic studies (typically 1-30 mg/kg). Behavioral tests (e.g., open field, elevated plus maze, novel object recognition) are conducted to assess cognitive enhancement, anxiolytic effects, or wake-promoting effects. Brain histamine levels are measured post-mortem by HPLC. Sleep-wake cycles are monitored by EEG/EMG. Specific protocols using Thioperamide are not extensively documented in the available literature. The compound's brain permeability makes it suitable for central nervous system studies. |
| ADME/Pharmacokinetics |
Thioperamide is orally active and brain-permeable, suggesting good oral bioavailability and blood-brain barrier penetration. The compound has a molecular weight of 292.4 g/mol. Detailed pharmacokinetic parameters (absorption, distribution, metabolism, excretion, half-life, Cmax, Tmax, AUC) are not extensively characterized in the available literature. As a small molecule antagonist, it would be expected to be well absorbed and distributed into the central nervous system. The compound's ability to cross the blood-brain barrier is supported by its central effects.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for Thioperamide are not extensively provided in the available literature. As a histamine H3/H4 receptor antagonist, it would be expected to have a safety profile related to modulation of histaminergic neurotransmission. The compound is orally active and brain-permeable, suggesting it can reach therapeutic concentrations in the central nervous system. Standard toxicology assessments would be required for therapeutic development, including acute, subchronic, and chronic toxicity studies, as well as genotoxicity and reproductive toxicity evaluations. No specific toxicity data are reported in the available references.
|
| References |
|
| Additional Infomation |
Thioperamide is a primary fatty amine.
Thioperamide (MR-12842) is a potent, orally active, and brain-permeable selective histamine H3 receptor antagonist. It inhibits [³H]histamine release with a Ki of 4.3 nM and inhibits [³H]histamine synthesis with a Ki of 31 nM. The compound also acts as a histamine H4 receptor antagonist/inverse agonist with Ki values of 25 and 27 nM for human recombinant H3 and H4 receptors, respectively. Thioperamide negatively regulates histamine release and enhances histaminergic neuron activity by blocking autoreceptors. No approved therapeutic status is reported. The compound is widely used as a research tool for studying histamine receptor pharmacology. |
| Molecular Formula |
C15H24N4S
|
|---|---|
| Molecular Weight |
408.51500
|
| Exact Mass |
408.183
|
| CAS # |
106243-16-7
|
| PubChem CID |
3035905
|
| Appearance |
White to off-white solid powder
|
| Density |
1.2 g/cm3
|
| Boiling Point |
499.5ºC at 760 mmHg
|
| Flash Point |
255.9ºC
|
| Vapour Pressure |
4.12E-10mmHg at 25°C
|
| Index of Refraction |
1.614
|
| LogP |
2.836
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
20
|
| Complexity |
322
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
QKDDJDBFONZGBW-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C15H24N4S/c20-15(18-13-4-2-1-3-5-13)19-8-6-12(7-9-19)14-10-16-11-17-14/h10-13H,1-9H2,(H,16,17)(H,18,20)
|
| Chemical Name |
N-cyclohexyl-4-(1H-imidazol-5-yl)piperidine-1-carbothioamide
|
| 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 |
| 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 | 2.4479 mL | 12.2393 mL | 24.4786 mL | |
| 5 mM | 0.4896 mL | 2.4479 mL | 4.8957 mL | |
| 10 mM | 0.2448 mL | 1.2239 mL | 2.4479 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
