| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Methiothepin mesylate targets multiple serotonin (5‑HT) receptor subtypes. It is a potent antagonist at 5‑HT₂ receptors with reported pKd values of 7.10 (5‑HT₁A), 7.28 (5‑HT₁B), 7.56 (5‑HT₁C), 6.99 (5‑HT₁D), 7.0 (5‑HT₅A), 7.8 (5‑HT₅B), 8.74 (5‑HT₆), and 8.99 (5‑HT₇). Additionally, it displays pKi values of 8.50 (5‑HT₂A), 8.68 (5‑HT₂B), and 8.35 (5‑HT₂C). Its broad‑spectrum antagonism makes it a valuable tool for dissecting serotonin receptor function and downstream signaling pathways.
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| ln Vitro |
Thiotipine mesylate is a 5-HT receptor antagonist, exhibiting pKds of 7.10, 7.28, 7.56 and 6.99 for 5-HT1A, 5HT1Bd, 5HT1C and 5HT1D respectively [1]. The pKd for 5-HT5A, 5-HT5B, 5-HT6 and 5-HT7 are 7.0, 7.8, 8.74 and 8.99 respectively [2]. Thiotipine displays significant affinity on 5-HT2A, 5HT2B and 5HT2C, with pKi of 8.50, 8.68 and 8.35 respectively [3].
In vitro, Methiothepin mesylate acts as a potent and non‑selective antagonist at cloned human 5‑HT receptors, as demonstrated by radioligand binding assays. It inhibits 5‑HT‑mediated functional responses such as cAMP accumulation, calcium mobilization, and inositol phosphate production in cells expressing specific receptor subtypes. The compound displays high affinity for most 5‑HT receptors, with pKd/pKi values in the nanomolar to sub‑nanomolar range, confirming its broad antagonistic profile. It is often used as a reference compound to block serotonergic signaling in cell‑based assays. |
| ln Vivo |
In vivo, Methiothepin mesylate has been used in serotonin (5‑HT) antagonist bioassays to explore the physiological and behavioral roles of 5‑HT receptors. It has been administered to rodents to study its effects on locomotion, anxiety‑like behavior, and thermoregulation. By blocking multiple 5‑HT receptor subtypes, it modulates serotonin‑mediated functions in the central nervous system and periphery. It has also been used to investigate the relationship between circulating cells and the hematopoietic niche.
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| Enzyme Assay |
In vitro receptor binding assays for Methiothepin mesylate are performed using radioligand binding with [³H]‑5‑HT or selective radioligands for specific 5‑HT receptor subtypes. Membrane preparations from recombinant cells or native tissues expressing the receptor of interest are incubated with varying concentrations of the compound and a fixed concentration of the radioligand. After incubation, bound radioactivity is measured by filtration or scintillation counting. Competition curves are generated, and pKd or pKi values are calculated by nonlinear regression analysis using appropriate binding models.
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| Cell Assay |
In vitro cellular assays for Methiothepin mesylate are conducted using cell lines stably expressing specific 5‑HT receptor subtypes (e.g., HEK‑293 or CHO cells). Cells are pre‑incubated with compound concentrations ranging from 0.1 nM to 100 µM for 15‑30 minutes, then stimulated with a selective agonist (e.g., 5‑HT or specific ligands). Functional readouts include cAMP accumulation (for Gαi‑coupled receptors), intracellular calcium flux (for Gαq‑coupled receptors), or reporter gene activity (e.g., luciferase under CRE or SRE control). Antagonist potency (pA₂ or IC₅₀) is determined from inhibition curves.
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| Animal Protocol |
In vivo animal studies for Methiothepin mesylate are conducted in rodent models (mice or rats) to evaluate its pharmacological effects on behavior, thermoregulation, and neuroendocrine function. The compound is typically administered intraperitoneally (1‑10 mg/kg) or subcutaneously. Behavioral tests such as open field, elevated plus maze, and forced swim test are performed to assess anxiety‑ and depression‑like phenotypes. Body temperature is monitored to evaluate 5‑HT‑mediated thermoregulation. Plasma corticosterone or prolactin levels may be measured as endocrine endpoints. Dose‑response and time‑course studies are performed to characterize in vivo potency and duration of action.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Methiothepin mesylate are not fully characterized in the public domain. The compound has a molecular weight of 452.65 and is soluble in DMSO and water (as mesylate salt). It is known to cross the blood‑brain barrier due to its lipophilic nature, enabling central effects after systemic administration. However, detailed parameters such as half‑life, bioavailability, volume of distribution, and metabolic pathways have not been systematically reported. Standard pharmacokinetic studies in rodents (intravenous and oral administration) would be required to establish its ADME profile.
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| Toxicity/Toxicokinetics |
Toxicological data for Methiothepin mesylate are limited, as it is exclusively a research tool and not intended for clinical use. No acute toxicity data have been published. At pharmacological doses (1‑10 mg/kg in rodents), it does not produce overt signs of toxicity, but high doses may cause sedation or hypothermia due to extensive 5‑HT receptor blockade. Standard safety pharmacology and repeat‑dose toxicity studies have not been performed. As with all research chemicals, appropriate laboratory safety measures should be followed.
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| References |
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| Additional Infomation |
Methiothepin mesylate is a potent, non‑selective serotonin receptor antagonist with high affinity for multiple 5‑HT subtypes (pKd/pKi ranging from 6.99 to 8.99). It is widely used as a pharmacological tool to study serotonin receptor function in vitro and in vivo. It is not approved for human therapy and has no clinical indications. Its structural formula is C₂₁H₂₈N₂O₃S₃, and it is supplied as a mesylate salt for enhanced solubility. It remains a key reference compound in neuropharmacology for characterizing serotonergic pathways.
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| Molecular Formula |
C20H24N2S2.CH4O3S
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| Molecular Weight |
452.65362
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| Exact Mass |
452.126
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| CAS # |
74611-28-2
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| Related CAS # |
Methiothepin maleate;19728-88-2
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| PubChem CID |
3039995
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| Appearance |
White to light yellow solid powder
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| LogP |
4.864
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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 |
2
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| Heavy Atom Count |
29
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| Complexity |
503
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCN(CC1)C2CC3=CC=CC=C3SC4=C2C=C(C=C4)SC.CS(=O)(=O)O
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| InChi Key |
CZMDZGZYKOGLJY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H24N2S2.CH4O3S/c1-21-9-11-22(12-10-21)18-13-15-5-3-4-6-19(15)24-20-8-7-16(23-2)14-17(18)20;1-5(2,3)4/h3-8,14,18H,9-13H2,1-2H3;1H3,(H,2,3,4)
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| Chemical Name |
methanesulfonic acid;1-methyl-4-(3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-5-yl)piperazine
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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) |
DMSO : ~62.5 mg/mL (~138.08 mM)
H2O : ~50 mg/mL (~110.46 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (220.92 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2092 mL | 11.0461 mL | 22.0921 mL | |
| 5 mM | 0.4418 mL | 2.2092 mL | 4.4184 mL | |
| 10 mM | 0.2209 mL | 1.1046 mL | 2.2092 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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