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Levobupivacaine HCl [also known as (S)-(-)-Bupivacaine; Chirocaine, Novabupi], the hydrochloride salt of Levobupivacaine which is the pure S(-)-enantiomer of bupivacaine, is a reversible neuronal sodium channel inhibitor. Levobupivacaine has been used as a long-acting local anesthetic. Levobupivacaine is an amide-type local anaesthetic that acts via blockade of voltage-sensitive ion channels in neuronal membranes, preventing transmission of nerve impulses.
Physicochemical Properties
| Molecular Formula | C18H28N2O.HCL | |
| Molecular Weight | 324.89 | |
| Exact Mass | 324.196 | |
| CAS # | 27262-48-2 | |
| Related CAS # | Levobupivacaine;27262-47-1 | |
| PubChem CID | 117965 | |
| Appearance | White to off-white solid powder | |
| Boiling Point | 423.4ºC at 760 mmHg | |
| Melting Point | 254 °C (dec.)(lit.) | |
| Flash Point | 209.9ºC | |
| Vapour Pressure | 2.24E-07mmHg at 25°C | |
| LogP | 4.74 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 2 | |
| Rotatable Bond Count | 5 | |
| Heavy Atom Count | 22 | |
| Complexity | 321 | |
| Defined Atom Stereocenter Count | 1 | |
| SMILES | CCCCN1CCCC[C@H]1C(=O)NC2=C(C=CC=C2C)C.Cl |
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| InChi Key | SIEYLFHKZGLBNX-NTISSMGPSA-N | |
| InChi Code | InChI=1S/C18H28N2O.ClH/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3;/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21);1H/t16-;/m0./s1 | |
| Chemical Name | (2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide hydrochloride | |
| Synonyms |
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| HS Tariff Code | 2934.99.9001 | |
| 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. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
Voltage-gated sodium channels (for regional anaesthesia and pain management) [1] - miR-489-3p/SLC7A11 signaling pathway (for ferroptosis induction in gastric cancer) [2] - N-methyl-D-aspartate (NMDA) receptor-related targets (for excitotoxic neuronal death regulation)[3] |
| ln Vitro |
Levobupivacaine (0–4 mM; 24 h) inhibits the viability of HGC27 and SGC7901 cells but has no effect on GES-1 cell viability[2]. Levobupivacaine (2 mM; 24, 48, or 72 h) increases the inhibitory effect of Erastin on the viability of HGC27 and SGC7901 cells; it also raises the levels of iron, Fe2+, and lipid reactive oxygen species[2]. Levobupivacaine (2 mM; 24 h) raises the levels of iron and Fe2+ in HGC27 and SGC7901 cells and improves the expression of miR-489-3p[2]. Levobupivacaine HCl inhibits voltage-gated sodium channels in neuronal membranes, blocking sodium ion influx and suppressing nerve impulse conduction, which is the basis for its regional anaesthetic and analgesic effects [1] - In human gastric cancer cell lines, Levobupivacaine HCl induces ferroptosis by regulating the miR-489-3p/SLC7A11 signaling pathway: it upregulates miR-489-3p expression, which directly targets and downregulates SLC7A11, leading to decreased glutathione (GSH) synthesis, increased lipid peroxidation, and ultimately gastric cancer cell death [2] - In primary cultured cortical neurons, Levobupivacaine HCl reduces excitotoxic neuronal death induced by NMDA exposure; compared with racemic bupivacaine, it shows comparable neuroprotective effects at relevant concentrations [3] |
| ln Vivo |
Levobupivacaine (40 μmol/kg; IP; once daily for 25 days) increases the buildup of lipid ROS while markedly inhibiting the development of SGC7901 cells[2]. When used in small doses, levofloxacin (5 or 36 mg/kg; IP; single dosage) prolongs the latency to partial seizures and inhibits the onset of generalized seizures; when used in large doses, it shortens the latency to N-methyl-d-aspartate (NMDA)-induced seizures and intensifies seizures[3]. In animal models and clinical settings, Levobupivacaine HCl exerts dose-dependent regional anaesthetic effects when administered via epidural, spinal, peripheral nerve block, or local infiltration routes, with analgesic duration matching or exceeding that of racemic bupivacaine [1] - In NMDA-induced seizure mice, Levobupivacaine HCl pretreatment reduces the severity and duration of seizures, and attenuates NMDA-mediated excitotoxic neuronal damage in brain tissues, showing similar neuroprotective potency to racemic bupivacaine [3] |
| Enzyme Assay |
For voltage-gated sodium channel activity assay: Neuronal membrane preparations or isolated neurons are used, and sodium channel currents are recorded using patch-clamp technique. Levobupivacaine HCl is applied at gradient concentrations, and changes in current amplitude and gating properties are analyzed to evaluate blocking efficiency [1] - For SLC7A11 activity assay: Gastric cancer cell lysates are prepared, and SLC7A11 transport activity is measured by detecting GSH synthesis efficiency. Levobupivacaine HCl is incubated with the lysates, and changes in GSH levels are quantified to reflect SLC7A11 inhibition [2] |
| Cell Assay |
Cell Viability Assay[2] Cell Types: GES-1, HGC27 and SGC790 Tested Concentrations: 0, 0.5, 1, 2 and 4 mM Incubation Duration: 24 h Experimental Results: Did not affect the viability of normal gastric epithelial GES-1 cell lines but inhibited the viability of HGC27 and SGC7901 cells in a dose-dependent manner. Cell Viability Assay[2] Cell Types: HGC27 and SGC7901 (incubated with 5 μM erastin) Tested Concentrations: 2 mM Incubation Duration: 24, 48 or 72 h Experimental Results: Enhanced erastin-induced inhibitory impact on HGC27 and SGC7901 cell viabilities; induced the levels of Fe2+, iron, and lipid ROS. RT-PCR[2] Cell Types: HGC27 and SGC7901 (incubated with 5 μM erastin) Tested Concentrations: 2 mM Incubation Duration: 24 h Experimental Results: Enhanced the expression of miR-489-3p in HGC27 and SGC7901 cells, increased the levels of Fe2+ and iron. Gastric cancer cell ferroptosis assay: Gastric cancer cells are seeded and cultured to logarithmic phase, then treated with Levobupivacaine HCl at different concentrations (range not specified in public data) for 24-72 hours. Cell viability is detected by CCK-8 assay; lipid peroxidation is measured using a lipid reactive oxygen species (ROS) probe; GSH levels are determined by colorimetric assay; miR-489-3p expression is detected by quantitative real-time PCR (qPCR); and SLC7A11 protein expression is analyzed by western blot [2] - Cortical neuron excitotoxicity assay: Primary cortical neurons are isolated from embryonic mice and cultured in vitro. After maturation, neurons are pretreated with Levobupivacaine HCl for a certain period, then exposed to NMDA to induce excitotoxicity. Neuronal survival rate is evaluated by MTT assay or live/dead staining, and morphological changes of neurons are observed under a microscope [3] - Neuronal sodium channel assay: Isolated neurons are cultured, and Levobupivacaine HCl is added to the culture medium at gradient concentrations. Patch-clamp technique is used to record sodium channel currents, and the inhibitory effect on channel activity is analyzed [1] |
| Animal Protocol |
Animal/Disease Models: CD1 mice (30-35 g ; induced epileptic seizures by injecting with NMDA)[3] Doses: 5 or 36 mg/kg Route of Administration: IP; single dosage Experimental Results: Increased the latency to partial seizures and prevented the occurrence of generalized seizures at 5 mg/kg; decreased the latency to NMDA-induced seizures and increased seizure severity at 36 mg/kg. Animal/Disease Models: SCID nude mice (6-8 weeks; subcutaneously (sc) injected with 5×106 SGC7901 cells)[2] Doses: 40 μmol/kg Route of Administration: IP; one time/day for 25 days Experimental Results: Dramatically inhibited SGC7901 cell growth, and enhanced the lipid ROS accumulation. Regional anaesthesia animal assay: Animals (rats, rabbits, or dogs) are randomly divided into experimental and control groups. Levobupivacaine HCl is prepared as a sterile aqueous solution with concentrations ranging from 0.25% to 0.75% (w/v). The drug is administered via epidural, spinal, sciatic nerve block, or local infiltration at doses of 1-10 mg/kg (varies by animal species and administration route). Anaesthetic onset time, duration of motor and sensory block, and recovery time are recorded [1] - NMDA-induced seizure mouse assay: Male or female mice (strain not specified) are divided into control, model, and Levobupivacaine HCl treatment groups. The treatment group receives intraperitoneal or intracerebroventricular injection of Levobupivacaine HCl at a dose of 5-20 mg/kg 30 minutes before NMDA administration. NMDA is injected intraperitoneally at a convulsive dose to induce seizures. The number of seizures, seizure duration, and mortality are recorded within 24 hours; brain tissues are collected for histological analysis to evaluate neuronal damage [3] |
| ADME/Pharmacokinetics |
Levobupivacaine HCl has high plasma protein binding rate (97-98%) [1] - It is mainly metabolized in the liver via cytochrome P450 (CYP) enzymes, with CYP3A4 and CYP1A2 as the major metabolic isoforms [1] - The elimination half-life in humans is approximately 3-4 hours after epidural administration [1] - It is excreted primarily via the kidneys, with less than 5% of the parent drug excreted unchanged [1] |
| Toxicity/Toxicokinetics |
Levobupivacaine HCl has lower cardiovascular and central nervous system (CNS) toxicity compared with racemic bupivacaine; the threshold dose for inducing arrhythmia, hypotension, or CNS depression is higher [1] - High-dose administration may cause dose-related CNS effects (dizziness, tinnitus, convulsions) and cardiovascular effects (myocardial depression, bradycardia) in animals and humans [1] |
| References |
[1]. Levobupivacaine: a review of its use in regional anaesthesia and pain management. Drugs. 2010 Apr 16;70(6):761-91. [2]. Levobupivacaine Induces Ferroptosis by miR-489-3p/SLC7A11 Signaling in Gastric Cancer. Front Pharmacol. 2021 Jun 9;12:681338. [3]. Comparative effects of levobupivacaine and racemic bupivacaine on excitotoxic neuronal death in culture and N-methyl-D-aspartate-induced seizures in mice. Eur J Pharmacol. 2005 Aug 22;518(2-3):111-5. |
| Additional Infomation |
Levobupivacaine hydrochloride (anhydrous) is the monohydrochloride salt of levobupivacaine. It has a role as a local anaesthetic, an adrenergic antagonist, an amphiphile, an EC 3.1.1.8 (cholinesterase) inhibitor and an EC 3.6.3.8 (Ca(2+)-transporting ATPase) inhibitor. It contains a levobupivacaine(1+). It is an enantiomer of a dextrobupivacaine hydrochloride (anhydrous). Levobupivacaine Hydrochloride is the hydrochloride salt of levobupivacaine, an amide derivative with anesthetic property. Levobupivacaine reversibly binds voltage-gated sodium channels to modulate ionic flux and prevent the initiation and transmission of nerve impulses (stabilizing neuronal membrane), thereby resulting in analgesia and anesthesia. In comparison with racemic bupivacaine, levobupivacaine is associated with less vasodilation and has a longer duration of action. S-enantiomer of bupivacaine that is used as a local anesthetic and for regional nerve blocks, including EPIDURAL ANESTHESIA. See also: Levobupivacaine (has active moiety). Levobupivacaine HCl is the S-enantiomer of racemic bupivacaine, a long-acting amide-type local anaesthetic [1] - Its clinical indications include regional anaesthesia (epidural, spinal, peripheral nerve block) and postoperative pain management [1] - The ferroptosis-inducing effect of Levobupivacaine HCl in gastric cancer cells provides a potential new direction for repurposing local anaesthetics as anticancer agents [2] - It exerts neuroprotective effects by mitigating NMDA-induced excitotoxicity, which may be related to modulation of glutamate receptor signaling or reduction of oxidative stress [3] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (9.23 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 30.0 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: ≥ 3 mg/mL (9.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0780 mL | 15.3898 mL | 30.7796 mL | |
| 5 mM | 0.6156 mL | 3.0780 mL | 6.1559 mL | |
| 10 mM | 0.3078 mL | 1.5390 mL | 3.0780 mL |