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| 10mg |
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| Targets |
Human Endogenous Metabolite
GABA transaminase (GABA-T) and potentially GABA receptors (indirect). Homocarnosine TFA is an endogenous dipeptide that acts as an inhibitor of GABA transaminase (GABA-T), the enzyme responsible for the catabolism of gamma-aminobutyric acid (GABA). By inhibiting GABA-T, homocarnosine increases the concentration of GABA in the brain, leading to enhanced inhibitory neurotransmission. This mechanism contributes to its anticonvulsant and neuroprotective effects. Homocarnosine may also directly modulate GABA_A receptors, though with lower affinity than GABA itself. Additionally, it possesses antioxidant properties, scavenging reactive oxygen species (ROS) and reducing oxidative stress. The dipeptide is concentrated in the brain, especially in the substantia nigra and hippocampus. The TFA salt is used for research. |
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| ln Vitro |
Synthesized in a subgroup of GABAergic neurons, homocarnosine is an inhibitory neuromodulator that is a dipeptide of gamma-aminobutyric acid (GABA) and histidine [1]. Due to its structural resemblance to carnosine, homocarnosine is a powerful substitute for imidazole peptides in skeletal muscle. Homocarnosine shares a structure with carnosine and is made up of histidine and gamma-aminobutyric acid (GABA). The main distinction is that, in carnosine, GABA has one extra carbon atom than beta-alanine. Compared to carnosine, homocarnosine is more resilient to serum carnosinase breakdown. Homocarnosine functions as a neuroprotective agent in a variety of illness states and is only known to be present in the brain and cerebrospinal fluid. To a similar degree as carnosine, homocarnosine exhibits antioxidant activity and guards against oxidative DNA damage [2].
In vitro, Homocarnosine TFA (0.1-1000 uM) inhibits human recombinant GABA transaminase (GABA-T) in a concentration-dependent manner, with an IC50 reported in the low millimolar range (e.g., 2-5 mM). It acts as a competitive inhibitor. In primary neuronal cultures, homocarnosine (0.1-10 mM) increases the levels of GABA in the medium and inside cells, as measured by HPLC or ELISA. It also protects neurons against glutamate-induced excitotoxicity and oxidative stress. For example, in rat hippocampal slice cultures, homocarnosine (1-10 mM) reduces cell death induced by oxygen-glucose deprivation (OGD). The compound also inhibits the formation of advanced glycation end products (AGEs) and reduces reactive oxygen species (ROS) in neuronal cells. It is not cytotoxic at concentrations up to 10 mM. The TFA salt is water-soluble. In radioligand binding assays, homocarnosine shows weak affinity for GABA_A receptors (Ki >100 uM). Its primary mechanism is GABA-T inhibition. |
| ln Vivo |
In vivo, Homocarnosine TFA has anticonvulsant effects in animal models. In mice, intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) administration of homocarnosine (10-200 mg/kg) protects against seizures induced by pentylenetetrazole (PTZ) or maximal electroshock (MES). For example, in the PTZ seizure model, homocarnosine (100 mg/kg, i.p.) significantly increases the latency to clonic seizures and reduces mortality. The anticonvulsant effect is blocked by a GABA synthesis inhibitor, confirming GABAergic mediation. In a rat model of temporal lobe epilepsy (pilocarpine-induced status epilepticus), homocarnosine (50 mg/kg, i.p.) reduces seizure severity and cognitive deficits. It also exhibits neuroprotective effects in models of cerebral ischemia and traumatic brain injury. Additionally, homocarnosine increases brain GABA levels and reduces lipid peroxidation. The TFA salt is suitable for in vivo use after neutralization. It is not approved for human therapy; it is a research compound.
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| Enzyme Assay |
For non-cellular enzyme assays, use a GABA transaminase (GABA-T) inhibition assay. Prepare recombinant human GABA-T or rat brain mitochondrial extract. The reaction buffer: 50 mM Tris-HCl pH 8.6, 10 mM 2-mercaptoethanol, 5 mM alpha-ketoglutarate, and 0.1 mM pyridoxal phosphate. Incubate enzyme (0.1-1 U) with varying concentrations of Homocarnosine TFA (0.1-10 mM) for 10 min. Then add GABA (10-50 mM) as substrate and incubate for 30 min at 37degC. Terminate with 0.5 M HCl. Measure the product (succinic semialdehyde) using a spectrophotometric method (e.g., with NADPH and succinic semialdehyde dehydrogenase) or by HPLC. Calculate IC50 and Ki. For antioxidant activity, use an ABTS or DPPH radical scavenging assay; homocarnosine (0.1-10 mM) shows concentration-dependent scavenging. For binding to GABA_A receptors, perform a radioligand binding assay with [3H]-muscimol or [3H]-flunitrazepam using rat brain membranes; homocarnosine displacement should be weak (IC50 >100 uM).
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| Cell Assay |
For cellular assays, use primary rat cortical or hippocampal neurons. Seed cells in 6-well plates (1×10^6 cells/well) in neurobasal medium with B27 supplement. After 7 days in vitro (DIV7), treat cells with Homocarnosine TFA (0.1-10 mM) for 24-72 h. For GABA measurement, lyse cells in 0.1 M HCl, centrifuge, and measure GABA by HPLC or ELISA. Homocarnosine should increase GABA levels. For neuroprotection, induce excitotoxicity by adding glutamate (50-100 uM) for 24 h; pre-treat with homocarnosine (1-10 mM) for 2 h. Assess cell viability by MTT or LDH release. Homocarnosine should reduce cell death. For ROS measurement, treat cells with H2O2 (100 uM) for 6 h; add DCFH-DA (10 uM) and measure fluorescence. Homocarnosine reduces ROS. The TFA salt is soluble; prepare 100 mM stock in water (pH adjust to 7.4 with NaOH). Use vehicle control (water). All experiments in triplicate, repeat 3 times.
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| Animal Protocol |
For in vivo anticonvulsant studies, use male CD-1 mice (20-25 g). Dissolve Homocarnosine TFA in sterile saline, adjust pH to 7.0-7.5 (with NaOH). Administer intraperitoneally (i.p.) at doses of 50, 100, and 200 mg/kg (volume 10 mL/kg) 30 min prior to seizure induction. For the pentylenetetrazole (PTZ) model, inject PTZ (50 mg/kg, i.p.) and observe mice for 30 min. Record latency to first myoclonic jerk, clonic seizure, and tonic-clonic seizure; also record mortality. Homocarnosine should increase latency and reduce seizure severity. For the maximal electroshock (MES) model, apply corneal electrodes (50 mA, 0.2 sec, 60 Hz). Measure hindlimb tonic extension (HLTE). Homocarnosine reduces HLTE duration. For GABA measurement, sacrifice mice after treatment, dissect brain (hippocampus, cortex), homogenize in 0.1 M HCl, and measure GABA by HPLC. Homocarnosine (200 mg/kg) should increase brain GABA levels by 30-50%. All animal procedures require IACUC approval. The compound is well-tolerated; no overt toxicity at these doses.
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| ADME/Pharmacokinetics |
No specific PK data for homocarnosine TFA are available. As a dipeptide (MW ≈ 300), homocarnosine has limited oral bioavailability and is rapidly cleared from plasma (t1/2 ≈ 15-30 min in rodents) due to hydrolysis by peptidases and renal excretion. Following i.p. administration in mice, it reaches peak plasma concentration within 30 min. It can cross the blood-brain barrier (BBB) to some extent, but the concentration in brain is much lower than in plasma. The TFA salt does not affect PK. For PK studies, administer 100 mg/kg i.p., collect blood at 0, 15, 30, 60, 120 min, and measure homocarnosine by LC-MS/MS. The compound is primarily excreted unchanged in urine. It is not a drug; detailed PK not required for research.
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| Toxicity/Toxicokinetics |
Homocarnosine has low acute toxicity. In mice, the i.p. LD50 is >500 mg/kg. At high doses (≥400 mg/kg), mild sedation and ataxia may occur due to excessive GABA elevation. No organ toxicity, genotoxicity, or carcinogenicity has been reported. In vitro, homocarnosine (up to 10 mM) is not cytotoxic to neurons. The TFA salt is non-toxic at the doses used. Standard laboratory safety precautions should be used. The compound is for research only, not for human therapy. Homocarnosine is also an endogenous metabolite; it is generally considered safe.
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| References | |
| Additional Infomation |
Homocarnosine (gamma-aminobutyryl-L-histidine) is a naturally occurring dipeptide enriched in the brain, particularly in the hippocampus and substantia nigra. It is synthesized from GABA and histidine by homocarnosine synthase. Homocarnosine is known to inhibit GABA transaminase, leading to elevated GABA levels and anticonvulsant effects. It also possesses antioxidant properties and can inhibit the formation of advanced glycation end products. It has been studied as a potential therapeutic for epilepsy, stroke, and neurodegenerative diseases such as Alzheimer's and Parkinson's. However, it is not an approved drug. The TFA salt is for research use only. This product is supplied as a lyophilized powder and should be stored at -20degC.
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| Molecular Formula |
C12H17F3N4O5
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| Molecular Weight |
354.28
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| CAS # |
2991254-59-0
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| Related CAS # |
Homocarnosine;3650-73-5
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| Appearance |
White to off-white 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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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) |
H2O :~125 mg/mL (~352.83 mM)
DMSO :~100 mg/mL (~282.26 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.06 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 25.0 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: ≥ 2.5 mg/mL (7.06 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 25.0 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: ≥ 2.5 mg/mL (7.06 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: 25 mg/mL (70.57 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 | 2.8226 mL | 14.1131 mL | 28.2263 mL | |
| 5 mM | 0.5645 mL | 2.8226 mL | 5.6453 mL | |
| 10 mM | 0.2823 mL | 1.4113 mL | 2.8226 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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