| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| ln Vitro |
Tipepidine reversibly inhibited dopamine (DA)-induced inward currents (IDA) mediated by D2 receptor-coupled GIRK channels in acutely dissociated rat ventral tegmental area (VTA) dopamine (DA) neurons, with an IC50 value of 7.0 μM. The inhibition was voltage-independent.
Under conventional whole-cell recording with intracellular perfusion of non-hydrolyzable GTPγS, tipepidine (30 μM) remarkably inhibited the irreversibly activated K+ current, suggesting its action likely at the level of the K+ channel itself or the G-protein/channel interaction. Tipepidine (10 μM) also inhibited baclofen-induced GIRK currents (IBaclofen) in VTA DA neurons, with an IC50 of 11.0 μM, indicating it can block GABAB receptor-mediated GIRK channels as well. In current-clamp recordings, application of tipepidine (10 μM) depolarized the membrane potential and generated action potentials in VTA DA neurons that had been hyperpolarized by DA, demonstrating an increase in neuronal excitability. [1] |
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| ln Vivo |
In the forced swim test, peptidine (ip; 10–40 mg/kg; 0.5–23 hours) dramatically shortened the immobility period for the ACTH-treated group. In treated cohorts, dipepidine (ip; 40 mg/kg) raises ACTH in the nucleus accumbens (
A single intraperitoneal (i.p.) injection of tipepidine (40 mg/kg) significantly increased the number of cells double-immunopositive for c-Fos and tyrosine hydroxylase (TH) in the VTA of rats, indicating activation of dopaminergic neurons. The same treatment also increased the number of c-Fos-positive but TH-negative cells in the VTA, suggesting potential activation of non-dopaminergic (e.g., GABAergic) neurons. [1] |
| Cell Assay |
Electrophysiological recordings on acutely dissociated neurons: VTA neurons were acutely dissociated from 8-15-day-old Wistar rats. Brain slices were treated with proteolytic enzymes (pronase and thermolysin). The VTA region was micro-punched and neurons were mechanically dissociated. Electrical measurements were performed using the nystatin-perforated whole-cell patch-clamp mode under voltage-clamp or current-clamp conditions. The external solution contained elevated K+ (20 mM) to facilitate analysis of inward rectifying K+ currents. Drugs were applied via a rapid "Y-tube" system. Dopamine-induced currents (IDA) were recorded, and the effects of tipepidine and other blockers were assessed. [1]
Immunohistochemistry for neuronal activation: Adult male Wistar rats were treated with a single i.p. injection of saline or tipepidine (40 mg/kg). Two hours post-injection, rats were perfused with paraformaldehyde. Brain sections (20 μm) containing the VTA were processed for double immunofluorescence staining. Sections were incubated with primary antibodies against c-Fos and tyrosine hydroxylase (TH), followed by appropriate fluorescent secondary antibodies. The number of double-positive (c-Fos+/TH+) and c-Fos+/TH- cells in the VTA was counted under a fluorescence microscope. [1] |
| Animal Protocol |
Animal/Disease Models: Male Wistar rats, body weight 150-240 g (5-7 weeks old) [2] Doses: 10, 20, and 40 mg/kg Mode of
Route of Administration: Extracellular dopamine levels in Ip; NAc) [2]. Results at 0.5, 5, and 23 hrs (hrs (hours)): ACTH-treated rats had diminished immobility time in the forced swim test. Protocol for immunohistochemistry study: Adult male Wistar rats (250-350 g) were housed under a 12-h light/dark cycle with free access to food and water. After acclimatization and handling, rats were randomly assigned to two groups (n=6 per group). One group received a single intraperitoneal (i.p.) injection of tipepidine citrate at a dose of 40 mg/kg, dissolved in saline. The control group received an equivalent volume of saline. Two hours after injection, animals were deeply anesthetized with sodium pentobarbital (50 mg/kg, i.p.) and transcardially perfused for brain collection and subsequent immunohistochemical analysis. [1] |
| References |
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| Additional Infomation |
Tiperidine is a centrally acting, non-narcotic antitussive that has been found to have novel antidepressant-like effects in animal models, such as the forced swimming test. The mechanism of its antidepressant-like effects and possible anxiolytic-like effects (in the marble-buried test) is thought to be related to the activation of the mesolimbic dopamine pathway. It is speculated that tiperidine activates dopamine neurons in the ventral tegmental area (VTA) by directly inhibiting GIRK channels coupled to inhibitory D2 autoreceptors and GABAB receptors. This inhibition leads to depolarization, increased firing of dopaminergic neurons, and subsequently increased dopamine release in the nucleus accumbens (NAc). The antidepressant-like effects of tiperidine can be blocked by dopamine D1 receptor antagonists, suggesting that its behavioral effects depend on stimulation of downstream D1 receptors in areas such as the NAc. [1]
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| Molecular Formula |
C15H18CLNS2
|
|---|---|
| Molecular Weight |
311.893120288849
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| Exact Mass |
311.056
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| CAS # |
1449686-84-3
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| Related CAS # |
Tipepidine;5169-78-8
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| PubChem CID |
138991192
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| Appearance |
Light yellow to brown solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
309
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.S1C=CC=C1/C(/C1=CC=CS1)=C1/CN(C)CCC/1
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| InChi Key |
MICLPSFJJVIDJE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H17NS2.ClH/c1-16-8-2-5-12(11-16)15(13-6-3-9-17-13)14-7-4-10-18-14;/h3-4,6-7,9-10H,2,5,8,11H2,1H3;1H
|
| Chemical Name |
3-(dithiophen-2-ylmethylidene)-1-methylpiperidine;hydrochloride
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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 : ~41.67 mg/mL (~133.60 mM)
H2O : ~3.33 mg/mL (~10.68 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.67 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 (6.67 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 (6.67 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: 33.33 mg/mL (106.86 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 | 3.2063 mL | 16.0313 mL | 32.0626 mL | |
| 5 mM | 0.6413 mL | 3.2063 mL | 6.4125 mL | |
| 10 mM | 0.3206 mL | 1.6031 mL | 3.2063 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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