Levobupivacaine

Levobupivacaine ((S)-(-)-Bupivacaine) is a long-acting amide local anaesthetic. Levobupivacaine exerts anaesthetic and analgesic effects through reversible blockade of neuronal sodium channel. Levobupivacaine can inhibit impulse transmission and conduction in cardiovascular and other tissues, possessing certain cardiac and CNS toxicity. Levobupivacaine is metabolized by hepatic cytochrome P450 (CYP450) enzymes in vivo. Levobupivacaine can also induce ferroptosis by miR-489-3p/SLC7A11 signaling in gastric cancer[1][2][3].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> Ferroptosis

Research Areas >> Neurological Disease

Sodium channels, Ferroptosis[1][2]

Levobupivacaine (0-4 mM; 24 h) does not affect the viability of GES-1 cells but inhibits the viability of HGC27 and SGC7901 cells[2]. Levobupivacaine (2 mM; 24, 48 or 72 h) enhances Erastin-induced inhibitory impact on HGC27 and SGC7901 cell viabilities; induces the levels of Fe2+, iron, and lipid ROS[2]. Levobupivacaine (2 mM; 24 h) enhances the expression of miR-489-3p in HGC27 and SGC7901 cells, increases the levels of Fe2+ and iron[2]. Cell Viability Assay[2] Cell Line: GES-1, HGC27 and SGC790 Concentration: 0, 0.5, 1, 2 and 4 mM Incubation Time: 24 h Result: 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 Line: HGC27 and SGC7901 (incubated with 5 μM erastin) Concentration: 2 mM Incubation Time: 24, 48 or 72 h Result: Enhanced erastin-induced inhibitory impact on HGC27 and SGC7901 cell viabilities; induced the levels of Fe2+, iron, and lipid ROS. RT-PCR[2] Cell Line: HGC27 and SGC7901 (incubated with 5 μM erastin) Concentration: 2 mM Incubation Time: 24 h Result: Enhanced the expression of miR-489-3p in HGC27 and SGC7901 cells, increased the levels of Fe2+ and iron.

Levobupivacaine (40 μmol/kg; IP; once daily for 25 days) significantly inhibits SGC7901 cell growth, and enhances the lipid ROS accumulation[2]. Levobupivacaine (5 or 36 mg/kg; IP; single dosage) increases the latency to partial seizures and prevents the occurrence of generalized seizures at low dosage; reduces the latency to N-methyl-d-aspartate (NMDA)-induced seizures and increased seizure severity at high dosage[3]. Animal Model: CD1 mice (30-35 g; induced epileptic seizures by injecting with NMDA)[3] Dosage: 5 or 36 mg/kg Administration: IP; single dosage Result: Increased the latency to partial seizures and prevented the occurrence of generalized seizures at 5 mg/kg; reduced the latency to NMDA-induced seizures and increased seizure severity at 36 mg/kg. Animal Model: SCID nude mice (6-8 weeks; subcutaneously injected with 5×106 SGC7901 cells)[2] Dosage: 40 μmol/kg Administration: IP; once daily for 25 days Result: Significantly inhibited SGC7901 cell growth, and enhanced the lipid ROS accumulation.

[1]. Sanford M, et al. Levobupivacaine: a review of its use in regional anaesthesia and pain management. Drugs. 2010 Apr 16;70(6):761-91.

[2]. Mao SH, et al. Levobupivacaine Induces Ferroptosis by miR-489-3p/SLC7A11 Signaling in Gastric Cancer. Front Pharmacol. 2021 Jun 9;12:681338.

[3]. Marganella C, et al. 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.

MOLECULAR FORMULA :

C18-H28-N2-O

MOLECULAR WEIGHT :

288.48

WISWESSER LINE NOTATION :

T6NTJ A4 BVMR B1 F1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

52 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 31,273,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

7200 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 31,273,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 31,273,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

9600 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 31,273,1972

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

9700 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 31,273,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>120 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,78,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intratracheal

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

14 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,78,1976