Levobupivacaine (0–4 mM; 24 hours) decreases the vitality of HGC27 and SGC7901 cells but has no effect on GES-1 cell viability [2]. Levobupivacaine (2 mM; 24, 48, or 72 hours) increases the levels of iron, Fe2+, and lipid ROS while amplifying the effects of Erastin-induced reduction of HGC27 and SGC7901 cell viability [2]. Levobupivacaine (2 mM; 24 h) raises Fe2+ and iron levels in HGC27 and SGC7901 cells while also enhancing the expression of miR-489-3p [2].

Levobupivacaine (40 μmol/kg; IP; once daily for 25 days) substantially reduces the development of SGC7901 cells and increases the buildup of lipid reactive oxygen species [2]. At low dosages, levofloxacin (5 or 36 mg/kg; IP; single dose) prolongs the latency of partial seizures and delays the start of generalized seizures; at high doses, it decreases the latency of N-methyl-d-aspartate (NMDA)-induced seizures and intensifies them [3].

Cell viability assay [2]
Cell Types: GES-1, HGC27 and SGC790
Tested Concentrations: 0, 0.5, 1, 2 and 4 mM
Incubation Duration: 24 hrs (hours)
Experimental Results: Does not affect the viability of normal gastric epithelial GES-1 cell line, but Inhibits the viability of HGC27 and SGC7901 cells in a dose-dependent manner.

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Cell viability assay [2]
Cell Types: HGC27 and SGC7901 (incubated with 5 μMerastin)
Tested Concentrations: 2 mM
Incubation Duration: 24, 48 or 72 hrs (hours)
Experimental Results: Enhanced erastin-induced inhibition of HGC27 and SGC7901 cell viability; induced Fe2+ , iron and lipid ROS levels.

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RT-PCR[2]
Cell Types: HGC27 and SGC7901 (incubated with 5 μMerastin)
Tested Concentrations: 2 mM
Incubation Duration: 24 hrs (hours)
Experimental Results: Enhanced expression of miR-489-3p, increased Fe2+ levels and iron in HGC27 and SGC7901 cells.

Animal/Disease Models: CD1 mice (30-35g; seizures induced by injection of NMDA) [3]
Doses: 5 or 36 mg/kg
Route of Administration: IP; single dose
Experimental Results: 5 mg/kg increased partial seizure latency and Prevents generalized seizures; 36 mg/kg dose shortens NMDA-induced seizure latency and increases seizure severity.

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Animal/Disease Models: SCID nude mice (6-8 weeks; 5×106 SGC7901 cells injected subcutaneously (sc) (sc)) [2]
Doses: 40 μmol/kg
Route of Administration: IP; one time/day for 25 days.
Experimental Results: Dramatically inhibited the growth of SGC7901 cells. , and enhance lipid ROS accumulation.

Absorption, Distribution and Excretion
The plasma concentration of levobupivacaine following therapeutic administration depends on dose and also on route of administration, because absorption from the site of administration is affected by the vascularity of the tissue. Peak levels in blood were reached approximately 30 minutes after epidural administration, and doses up to 150 mg resulted in mean Cmax levels of up to 1.2 µg/mL.
Following intravenous administration, recovery of the radiolabelled dose of levobupivacaine was essentially quantitative with a mean total of about 95% being recovered in urine and feces in 48 hours. Of this 95%, about 71% was in urine while 24% was in feces.
66.91 ±18.23 L [after intravenous administration of 40 mg in healthy volunteers]
39.06 ±13.29 L/h [after intravenous administration of 40 mg in healthy volunteers]

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Metabolism / Metabolites
Levobupivacaine is extensively metabolized with no unchanged levobupivacaine detected in urine or feces. In vitro studies using [14 C] levobupivacaine showed that CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. In vivo, the 3-hydroxy levobupivacaine appears to undergo further transformation to glucuronide and sulfate conjugates. Metabolic inversion of levobupivacaine to R(+)-bupivacaine was not evident both in vitro and in vivo.
Levobupivacaine has known human metabolites that include N-(2,6-Dimethylphenyl)piperidine-2-carboxamide.
Levobupivacaine is extensively metabolized with no unchanged levobupivacaine detected in urine or feces. In vitro studies using [14 C] levobupivacaine showed that CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. In vivo, the 3-hydroxy levobupivacaine appears to undergo further transformation to glucuronide and sulfate conjugates. Metabolic inversion of levobupivacaine to R(+)-bupivacaine was not evident both in vitro and in vivo.
Route of Elimination: Following intravenous administration, recovery of the radiolabelled dose of levobupivacaine was essentially quantitative with a mean total of about 95% being recovered in urine and feces in 48 hours. Of this 95%, about 71% was in urine while 24% was in feces.
Half Life: 3.3 hours

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Biological Half-Life
3.3 hours

Toxicity Summary
Levobupivacaine is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Levobupivacaine is no longer marketed in the US. Levels in breastmilk are low, and it is poorly absorbed orally by the infant. Bupivacaine, the racemic mixture of dextro- and levobupivacaine, has not caused any adverse effects in breastfed infants.
Local anesthetics during labor and delivery with other anesthetics and analgesics has been reported by some to interfere with breastfeeding. However, this assessment is controversial and complex because of the many different combinations of drugs, dosages and patient populations studied as well as the variety of techniques used. In contrast, epidural local anesthetics begun after clamping of the umbilical cord appears to enhance breastfeeding success because of improved pain control. Overall, it appears that with good breastfeeding support epidural levobupivacaine with or without fentanyl or one of its derivatives has little or no adverse effect on breastfeeding success. Labor Labor pain medication may delay the onset of lactation. In one study, adding levobupivacaine wound infiltration to multimodal analgesia after cesarean section improved breastfeeding comfort.
◉ Effects in Breastfed Infants
Relevant published information on levobupivacaine was not found as of the revision date. However, bupivacaine administered to the mother by intrapleural or epidural routes had no effect on 13 breastfed infants.
◉ Effects on Lactation and Breastmilk
A nonrandomized convenience sample of women who did (n = 209) or did not (n = 157) receive epidural analgesia during labor was analyzed to determine whether epidurals affected the onset of lactation. Although not standardized, the typical procedure used sufentanil 10 to 15 mg together with either ropivacaine 0.1% or levobupivacaine 0.0625% epidurally, supplemented by epidural boluses of ropivacaine 0.1% or levobupivacaine 0.0625% about every 2 hours. No difference was found in the time of lactation onset between the two groups. Although women in both groups stated they wished to breastfeed prior to delivery, exclusive breastfeeding at 20 days postpartum was less frequent in the women who received an epidural (43%) than in women who did not (57%).
A randomized, unblinded study of women undergoing cesarean section found that women who received postoperative wound infiltration with levobupivacaine. A bolus of 50 mg was infused subfascially 5 cm lateral to the wound incision, followed by 6.25 mg/hour for 48 hours. Additional analgesia included acetaminophen, celecoxib, nefopam, morphine and droperidol. On day 2 postpartum, women who received the levobupivacaine infusion reported more comfort with breastfeeding. More women who received the levobupivacaine were breastfeeding on day 2, but the difference was not statistically significant.
A retrospective medical record study in China compared women who received patient-controlled epidural analgesia during labor (n = 527) to those who did not (n = 395). Epidural analgesia included 0.1% levobupivacaine and 5 mg of sufentanil in 10 mL of saline. All women completed a questionnaire regarding their breastfeeding experience at 6 months postpartum. There were no statistically significant differences between the groups in the proportion who initiated breastfeeding within 1 hour after birth or who exclusively or partially breastfed their infants at 1, 3, or 6 months postpartum.

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Protein Binding
>97%

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Toxicity Data
LD50: 5.1mg/kg in rabbit, intravenous; 18mg/kg in rabbit, oral; 207mg/kg in rabbit, parenteral; 63mg/kg in rat, subcutaneous.

[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.

Levobupivacaine is the (S)-(-)-enantiomer of bupivacaine. 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 is a conjugate base of a levobupivacaine(1+). It is an enantiomer of a dextrobupivacaine.
Levobupivacaine is an amino-amide local anaesthetic drug belonging to the family of n-alkylsubstituted pipecoloxylidide. It is the S-enantiomer of bupivacaine. Levobupivacaine hydrochloride is commonly marketed by AstraZeneca under the trade name Chirocaine. In particular, the specific levobupivacaine enantiomer is a worthwhile pursuit because it demonstrates less vasodilation and possesses a greater length of action in comparison to bupivacaine. It is approximately 13 per cent less potent (by molarity) than racemic bupivacaine.Levobupivacaine is indicated for local anaesthesia including infiltration, nerve block, ophthalmic, epidural and intrathecal anaesthesia in adults; and infiltration analgesia in children. When administered appropriately, the occurrence of adverse effects is not anticipated much if at all. In general, the majority of potential adverse effects are predominantly associated with inappropriate administration methods that may cause systemic exposure and/or toxicity associated with overexposure to an anesthetic. Regardless, allergic reactions may also occur - although only rarely.
Levobupivacaine is an amino-amide local anaesthetic drug belonging to the family of n-alkylsubstituted pipecoloxylidide. It is the S-enantiomer of bupivacaine. Levobupivacaine hydrochloride is commonly marketed by AstraZeneca under the trade name Chirocaine. Compared to bupivacaine, levobupivacaine is associated with less vasodilation and has a longer duration of action. It is approximately 13 per cent less potent (by molarity) than racemic bupivacaine.Levobupivacaine is indicated for local anaesthesia including infiltration, nerve block, ophthalmic, epidural and intrathecal anaesthesia in adults; and infiltration analgesia in children. Adverse drug reactions (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however allergic reactions can rarely occur. [Wikipedia]
S-enantiomer of bupivacaine that is used as a local anesthetic and for regional nerve blocks, including EPIDURAL ANESTHESIA.

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Drug Indication
For the production of local or regional anesthesia for surgery and obstetrics, and for post-operative pain management
FDA Label

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Mechanism of Action
Local anesthetics such as Levobupivacaine block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Specifically, the drug binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization.

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Pharmacodynamics
Levobupivacaine, a local anesthetic agent, is indicated for the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.

C18H28N2O

288.43

288.22

27262-47-1

Levobupivacaine hydrochloride;27262-48-2

92253

Typically exists as solid at room temperature

1.0±0.1 g/cm3

423.4±45.0 °C at 760 mmHg

254ºC (dec.)(lit.)

209.9±28.7 °C

0.0±1.0 mmHg at 25°C

1.547

3.64

1

2

5

21

321

1

CCCCN1CCCC[C@H]1C(NC2=C(C=CC=C2C)C)=O

LEBVLXFERQHONN-INIZCTEOSA-N

InChI=1S/C18H28N2O/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)/t16-/m0/s1

(2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.)