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| 1mg |
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| Targets |
T-type calcium channels (Cav3.1, Cav3.2, Cav3.3), low voltage-activated calcium channels that play critical roles in neuronal excitability, cardiac pacemaking, and cellular proliferation. TTA-P2 is a potent inhibitor of T-type calcium channels, blocking both wild-type and mutant Cav3.1 channels. The R-enantiomer is the active form, used to study the physiological and pathophysiological roles of T-type calcium channels in various tissues and disease states.
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| ln Vitro |
In vitro, TTA-P2 potently inhibits T-type calcium channel currents. In electrophysiological recordings from deep cerebellar nuclear neurons, TTA-P2 completely abolishes window currents for both wild-type and mutant Cav3.1 channels. The compound shows high selectivity for T-type channels over other voltage-gated calcium channels (L-type, N-type, P/Q-type, R-type). The (R)-enantiomer is the primary active form used in functional studies.
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| ln Vivo |
In vivo, TTA-P2 penetrates well into the CNS following systemic administration, making it a useful tool for studying T-type channel function in awake animals. Because T-type channels are involved in absence epilepsy, pain, sleep rhythms, and cardiac function, TTA-P2 has been used in rodent models to study these processes. In animal models of pain, T-type channel inhibition produces analgesic effects. The compound is also used as a research tool to investigate the role of T-type channels in neuropsychiatric disorders.
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| Enzyme Assay |
Whole-cell patch-clamp electrophysiology is performed using heterologous expression systems (HEK293 cells expressing Cav3.1, Cav3.2, or Cav3.3 channels) or acutely dissociated native neurons (e.g., from deep cerebellar nuclei, thalamus, or dorsal root ganglia). Cells are voltage-clamped at a holding potential of -100 mV. TTA-P2 is applied extracellularly at varying concentrations (0.01-10 uM), and T-type currents are evoked by depolarizing voltage steps to -30 mV. Current inhibition is measured to determine IC50.
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| Cell Assay |
For neuronal activity studies, primary neuronal cultures (e.g., thalamic neurons or cerebellar granule neurons) are used. Cells are loaded with a calcium-sensitive dye (e.g., Fluo-4 AM). Neuronal activity is evoked by KCl depolarization or electrical field stimulation in the presence or absence of (R)-TTA-P2. Intracellular calcium transients are measured using fluorescence microscopy. For proliferation studies, cancer cell lines expressing T-type channels are treated with TTA-P2, and cell viability is assessed by MTT assay.
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| Animal Protocol |
TTA-P2 is used in rodent models of absence epilepsy, neuropathic pain, and other disorders involving T-type channel dysfunction. Male rats or mice are administered (R)-TTA-P2 via intraperitoneal (IP) injection (doses 1-30 mg/kg) or oral gavage. For epilepsy studies, electroencephalogram (EEG) recordings are performed to measure spike-wave discharge frequency. For pain studies, mechanical allodynia and thermal hyperalgesia are assessed using von Frey filaments and Hargreaves apparatus. Behavioral tests include rotarod for motor coordination.
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| ADME/Pharmacokinetics |
(R)-TTA-P2 is highly lipophilic and readily crosses the blood-brain barrier (BBB) due to its favorable physicochemical properties. Following systemic administration, brain concentrations achieve levels sufficient for robust T-type channel inhibition. The compound has good metabolic stability in liver microsomes and a moderate plasma half-life suitable for in vivo pharmacology studies (typically 2-6 hours in rodents). Detailed PK parameters such as clearance, volume of distribution, and oral bioavailability are not fully publicly available for this research compound.
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| Toxicity/Toxicokinetics |
In animal studies, TTA-P2 is generally well-tolerated at effective doses (1-10 mg/kg IP). Potential side effects of T-type channel inhibition in animals include mild ataxia or sedation due to the role of T-type channels in thalamocortical rhythm generation, but these effects are dose-dependent and reversible. No significant hepatotoxicity, nephrotoxicity, or cardiac toxicity has been reported at the doses used for research purposes. Comprehensive chronic toxicology studies have not been published, as this is a research tool compound.
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| References |
[1]. Chemin J, et al. De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene. Brain. 2018;141(7):1998-2013.
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| Additional Infomation |
(R)-TTA-P2 is a research-grade chemical used as a selective pharmacological tool to inhibit T-type calcium channels. TTA-P2 was developed as a more potent and selective alternative to earlier T-type channel blockers like mibefradil. T-type calcium channels are validated drug targets for absence epilepsy (ethosuximide) and are being investigated for pain, hypertension, cancer, and sleep disorders. This product is for research use only and has not been approved by the FDA or other regulatory agencies for human therapeutic use.
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| Molecular Formula |
C21H29CL2FN2O2
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|---|---|
| Molecular Weight |
431.37
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| Related CAS # |
TTA-P2;1072018-68-8
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| Appearance |
Off-white to light yellow solid powder
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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 |
| 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 :~50 mg/mL (~115.91 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 | 2.3182 mL | 11.5910 mL | 23.1820 mL | |
| 5 mM | 0.4636 mL | 2.3182 mL | 4.6364 mL | |
| 10 mM | 0.2318 mL | 1.1591 mL | 2.3182 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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