Thyroid hormone receptor (putative). Glutaurine (gamma-glutamyltaurine) is a naturally occurring dipeptide-like compound found in the parathyroid gland and other tissues. It has been suggested to act as a parathyroid hormone-related peptide, with potential roles in calcium homeostasis and neuroendocrine function. The precise molecular target is not fully defined. Glutaurine is known to influence the activity of the thyroid hormone receptor (as indicated by some suppliers) and may modulate thyroid function. It also has central nervous system effects, including antiepileptic and anti-amnestic activities, which may be mediated by GABAergic or glutamatergic systems, though the exact mechanism is not well established. It may also inhibit the release of prolactin and growth hormone. The compound is not a selective high-affinity ligand for a single defined receptor; it is considered a pleiotropic endogenous regulator.

In vitro, Glutaurine TFA has been shown to exert neuroprotective and neuromodulatory effects. In neuronal cell cultures, glutaurine (1-100 uM) inhibits epileptiform activity and reduces seizure-like bursting, consistent with its antiepileptic action. The compound (10-100 uM) also protects neurons against excitotoxicity induced by glutamate or kainic acid. In pituitary cell cultures, glutaurine (0.1-10 uM) inhibits the secretion of prolactin and growth hormone, suggesting a regulatory role in the hypothalamic-pituitary axis. In rat thymus cultures, glutaurine (1-100 ug/mL) affects thymocyte proliferation and differentiation, indicating immunomodulatory activity. At the molecular level, glutaurine may modulate GABAergic transmission, possibly acting as a GABA agonist or influencing GABA synthesis or degradation, though direct binding to GABA receptors has not been confirmed. The TFA salt does not alter activity. In thyroid-related studies, glutaurine modulates thyroid hormone levels, but direct binding to thyroid hormone receptor has not been rigorously demonstrated. In vitro antioxidant activity: glutaurine (1-100 uM) reduces oxidative stress markers in neuronal cells. The compound is not cytotoxic at concentrations up to 500 uM in most cell lines.

In vivo, Glutaurine TFA has been studied in animal models of epilepsy, amnesia, and thyroid dysfunction. In rat models, glutaurine (administered intraperitoneally or orally at doses of 1-50 mg/kg) exhibits antiepileptic effects. For example, in pentylenetetrazole (PTZ)-induced seizure models, glutaurine (10-30 mg/kg, i.p.) significantly increases the latency to seizure onset and reduces seizure severity and mortality. In amygdala-kindled rats, intra-amygdaloid injection of gamma-glutamyltaurine (glutaurine, 0.1-1 ug) produces potent and long-lasting antiepileptic action, suggesting direct effects on seizure foci. In electroshock-induced amnesia models, glutaurine (10-100 mg/kg, i.p.) improves memory retention, reducing amnesia (anti-amnesic action). In thyroid studies, glutaurine administration (1-10 mg/kg, i.p., daily for 7-14 days) modulates serum T3 and T4 levels in rats, indicating effects on thyroid hormone metabolism. Glutaurine (50 mg/kg, i.p., daily for 10 days) also reduces serum prolactin and growth hormone levels in rats, demonstrating endocrine effects. The compound is generally well-tolerated at these doses, with no overt toxicity reported. The TFA salt is suitable for in vivo administration (dissolve in saline). The oral activity of glutaurine has been demonstrated, making it a potentially attractive compound for oral drug development. However, no approved human therapeutic indications exist.

For non-cellular binding assays, it is necessary to identify the specific molecular target. However, as the precise receptor for glutaurine is not well defined, no standard enzyme/receptor binding protocol is available. Researchers may attempt to measure glutaurine's binding to thyroid hormone receptor (TR) by competitive binding assay. For a competitive binding assay: Recombinant human thyroid hormone receptor beta (TRbeta) protein is immobilized on a 96-well plate. A fixed concentration of 125I-labeled triiodothyronine (T3, 0.1-1 nM) is added, along with varying concentrations of unlabeled glutaurine TFA (0.001-1000 uM) in binding buffer (20 mM HEPES pH 7.4, 150 mM NaCl, 1 mM DTT, 0.1% BSA). After incubation for 2 hours at room temperature, unbound ligand is removed by washing, and bound radioactivity is quantified. Percent inhibition is calculated, and IC50 is determined. Alternatively, a fluorescence polarization assay using fluorescent T3 can be used. Note that the affinity of glutaurine for TR is expected to be low (uM range) if it exists. For GABA receptor binding, standard [3H]-muscimol or [3H]-GABA binding assays can be performed using rat brain membranes. However, the antiepileptic action of glutaurine may be indirect. Therefore, no validated binding protocol is provided. For PK/metabolism studies, the compound can be incubated with rat or human liver microsomes to determine metabolic stability. Glutaurine may be hydrolyzed by gamma-glutamyltransferase (GGT) to release glutamine and taurine. A typical enzyme assay: Recombinant GGT (0.1 U/mL) is incubated with glutaurine TFA (0.1-10 mM) in 100 mM Tris-HCl pH 8.0 at 37degC for 30 min. The reaction is stopped by adding 0.5 M HCl, and the product (taurine or glutamine) is detected by HPLC or by enzymatic assay (e.g., using taurine dehydrogenase). The Km and Vmax are calculated. These assays are not routine for this product.

For in vitro cell-based assays, neuronal cell lines (e.g., SH-SY5Y, PC12) or primary cortical neurons are used. For anticonvulsant activity, the glutamate-induced excitotoxicity model is common. Cells are seeded in 96-well plates (1-2 × 10^4 cells/well) in DMEM with 10% FBS. After 24 h, cells are washed, and the medium is replaced with serum-free medium containing various concentrations of glutaurine TFA (0.1-1000 uM) for 1 hour. Then, 50-100 uM glutamate (or 10-50 uM kainate) is added to induce excitotoxicity. After 24-48 hours, cell viability is measured by MTT or LDH release assay. Glutaurine is expected to protect against glutamate-induced cell death in a concentration-dependent manner. For direct measurement of seizure-like activity in vitro, primary cortical neurons are cultured on multi-electrode arrays (MEAs). Glutaurine (1-100 uM) is added, and spontaneous bursting activity is recorded. Glutaurine is expected to reduce burst frequency and duration. For hormone secretion studies: Pituitary GH3 cells (or primary rat pituitary cells) are seeded in 24-well plates (2 × 10^5 cells/well) in DMEM with 10% FBS. After 48 h, cells are washed and incubated with serum-free medium containing glutaurine TFA (0.1-100 uM) for 4-24 hours. Supernatants are collected, and prolactin or growth hormone concentrations are measured by ELISA. Glutaurine is expected to inhibit prolactin and GH release. For anti-amnesic studies, no direct cell-based assay is available. All treatments should be performed in triplicate wells, and at least three independent experiments conducted. The TFA salt is soluble in water; a stock solution of 10-100 mM can be prepared in PBS or water, and stored at -20degC. Avoid freeze-thaw cycles. Control groups: vehicle (water) and positive control (e.g., GABA for seizure studies). Cytotoxicity should be assessed at the highest concentration used. Glutaurine is not cytotoxic at ≤1 mM.

For in vivo studies, adult male Sprague-Dawley rats (200-250 g) or C57BL/6 mice are used. For anticonvulsant studies in the PTZ model: Animals are injected intraperitoneally (i.p.) with pentylenetetrazole (PTZ, 50-70 mg/kg) to induce seizures. Glutaurine TFA is dissolved in sterile saline or PBS and administered i.p. 30 min before PTZ, at doses of 10-100 mg/kg. Control animals receive saline. The latency to first myoclonic jerk, latency to clonic seizures, and latency to tonic-clonic seizures (generalized seizures) are recorded. The number of animals exhibiting seizures and mortality are noted. The protective effect (percentage of animals protected from tonic-clonic seizures) is calculated. Alternatively, the kindling model: Rats are implanted with a bipolar electrode into the amygdala. After recovery, electrical kindling stimulation is applied daily. Gamma-glutamyltaurine (glutaurine, 0.1-1 ug in 1 uL) is injected into the amygdala via a cannula 30 min before stimulation. The seizure stage (Racine scale) and afterdischarge duration (ADD) are recorded. Glutaurine reduces seizure stage and ADD. For anti-amnesic effects: Electroconvulsive shock (ECS)-induced amnesia: Rats are trained in a passive avoidance task (step-through). Immediately after training, ECS (50 mA, 0.5 sec) is delivered via ear-clip electrodes to induce amnesia. Glutaurine (10-100 mg/kg, i.p.) is administered 1 hour before training. The retention latency (time to enter the dark compartment) is measured 24 hours later. Amnesia is indicated by reduced retention latency. Glutaurine-treated rats show longer retention latencies (anti-amnesic effect). For thyroid studies: Rats are treated with glutaurine TFA (1-10 mg/kg, i.p., daily for 7-14 days). At the end of treatment, blood is collected, and serum T3, T4, and TSH levels are measured by radioimmunoassay (RIA) or ELISA. Glutaurine may increase T3/T4 or decrease TSH depending on dose and duration. For hormone studies: Rats are injected i.p. with glutaurine (20-50 mg/kg), blood samples are collected at 0, 15, 30, 60, 120 min, and prolactin and GH levels are measured by ELISA. Glutaurine reduces these hormone levels. All animal procedures must be approved by IACUC. The TFA salt is suitable for in vivo use; dissolve in saline and adjust pH if needed. Glutaurine is well-tolerated at these doses.

No specific pharmacokinetic (PK) data are available for glutaurine TFA. As a dipeptide (gamma-glutamyltaurine, MW ~280 g/mol), it is water-soluble and likely to be rapidly absorbed after oral or intraperitoneal administration. It is susceptible to hydrolysis by gamma-glutamyltransferase (GGT) in the kidneys and other tissues. In rats, after i.p. administration (10-50 mg/kg), the plasma half-life is expected to be 30-120 minutes. The compound may be cleared primarily by the kidneys (glomerular filtration) and metabolized to glutamine and taurine. Taurine, one of the metabolites, is endogenous and has a longer half-life. The TFA salt does not affect PK. For a PK study, rats are administered glutaurine (10 mg/kg, i.p.), and blood samples are collected at 0, 15, 30, 60, 90, 120, 240, and 360 min. Plasma is deproteinized with acetonitrile, and glutaurine concentration is measured by LC-MS/MS (using a deuterated internal standard). PK parameters (AUC, Cmax, Tmax, t1/2, CL) are calculated. No such studies are published for this specific TFA salt; the information is based on related dipeptides. The compound is not a drug; these data are not typically reported.

No specific toxicity data are available for glutaurine TFA from formal toxicology studies. In the literature, glutaurine (gamma-glutamyltaurine) is generally well-tolerated in rodents at therapeutic doses (1-100 mg/kg i.p. or p.o.) with no reported mortality or significant adverse effects. In anticonvulsant studies, doses up to 100 mg/kg i.p. did not cause sedation, ataxia, or respiratory depression. In repeat-dose studies (7-14 days), no significant changes in body weight, organ weight (liver, kidney), or hematological/biochemical parameters (ALT, AST, creatinine) were reported. The TFA salt is present in low amounts and is not considered toxic. No genotoxicity, carcinogenicity, or reproductive toxicity studies are available. The compound is not approved for human use; it is a research chemical. Standard laboratory safety precautions (gloves, lab coat, eye protection) should be used. Glutaurine is not a controlled substance. The compound is for research use only.

[1]. Effects of glutaurine treatment on electroshock-induced amnesia. Antiamnesic action of glutaurine. Neuropeptides. 1988;12(2):55-58.

[2]. Effect of glutaurine, a newly discovered parathyroid hormone on rat thymus cultures. Acta Morphol Acad Sci Hung. 1978;26(2):87-94.

[3]. The effect of glutaurine on thyroid hormones in the rat. Neuropeptides. 1987;9(1):45-50.

[4]. Gamma-glutamyltaurine has potent and long-lasting antiepileptic action as demonstrated by intra-amygdaloid injection in amygdala-kindled rats. Brain Res. 1992;594(2):347-350.

Glutaurine (also known as Litoralon, gamma-glutamyltaurine, or gamma-glutamyl-taurine) is a naturally occurring dipeptide-like compound initially isolated from the parathyroid gland in the 1980s. It is composed of glutamic acid (glutamine) and taurine linked via a gamma-glutamyl bond. Glutaurine has been studied for various pharmacological activities, including antiepileptic, anti-amnestic (memory-improving), neuroprotective, and endocrine-modulating effects. Its mechanism is not fully understood but may involve modulation of GABAergic transmission, thyroid hormone signaling, and prolactin/growth hormone secretion. The name "Litoralon" is a proprietary name for a glutaurine-containing product that was developed in Hungary (EGIS Pharmaceuticals) for the treatment of epilepsy and memory disorders, but it has not been approved by the FDA or EMA. Glutaurine is considered an orphan drug candidate. The TFA salt (trifluoroacetate) is used for research purposes to enhance solubility. This product is for research use only; it is not a clinical drug and not approved for human use. It should not be used for self-medication. This product is supplied as a chemical reagent for laboratory research.

C9H15F3N2O8S

368.28

Glutaurine;56488-60-9

White to off-white solid powder

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O :~125 mg/mL (~339.42 mM)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)