scholarly journals Lido-OH, a Hydroxyl Derivative of Lidocaine, Produced a Similar Local Anesthesia Profile as Lidocaine With Reduced Systemic Toxicities

2021 ◽  
Vol 12 ◽  
Author(s):  
Qinqin Yin ◽  
Weiyi Zhang ◽  
Bowen Ke ◽  
Jin Liu ◽  
Wensheng Zhang
Keyword(s):  
Sciatic Nerve ◽  
Local Anesthesia ◽  
Nerve Block ◽  
Therapeutic Index ◽  
Negative Control ◽  
Sciatic Nerve Block ◽  
Dose Effect ◽  
Effective Doses ◽  
Block Models

Background: lidocaine is one of the most commonly used local anesthetics for the treatment of pain and arrhythmia. However, it could cause systemic toxicities when plasma concentration is raised. To reduce lidocaine’s toxicity, we designed a hydroxyl derivative of lidocaine (lido-OH), and its local anesthesia effects and systemic toxicity in vivo were quantitively investigated.Method: the effectiveness for lido-OH was studied using mouse tail nerve block, rat dorsal subcutaneous infiltration, and rat sciatic nerve block models. The systemic toxicities for lido-OH were evaluated with altered state of consciousness (ASC), arrhythmia, and death in mice. Lidocaine and saline were used as positive and negative control, respectively. The dose-effect relationships were analyzed.Results: the half effective-concentration for lido-OH were 2.1 mg/ml with 95% confident interval (CI95) 1.6–3.1 (lidocaine: 3.1 mg/ml with CI95 2.6–4.3) in tail nerve block, 8.2 mg/ml with CI95 8.0–9.4 (lidocaine: 6.9 mg/ml, CI95 6.8–7.1) in sciatic nerve block, and 5.9 mg/ml with CI95 5.8–6.0 (lidocaine: 3.1 mg/ml, CI95 2.4–4.0) in dorsal subcutaneous anesthesia, respectively. The magnitude and duration of lido-OH were similar with lidocaine. The half effective doses (ED50) of lido-OH for ACS was 45.4 mg/kg with CI95 41.6–48.3 (lidocaine: 3.1 mg/kg, CI95 1.9–2.9), for arrhythmia was 16.0 mg/kg with CI95 15.4–16.8 (lidocaine: 3.0 mg/kg, CI95 2.7–3.3), and for death was 99.4 mg/kg with CI95 75.7–124.1 (lidocaine: 23.1 mg/kg, CI95 22.8–23.4). The therapeutic index for lido-OH and lidocaine were 35.5 and 5.6, respectively.Conclusion: compared with lidocaine, lido-OH produced local anesthesia at similar potency and efficacy, but with significantly reduced systemic toxicities.

scholarly journals Ultralong Peripheral Nerve Block by Lidocaine:Prilocaine 1:1 Mixture in a Lipid Depot Formulation

2006 ◽  
Vol 104 (1) ◽  
pp. 110-121 ◽  
Author(s):  
Lars Söderberg ◽  
Henrik Dyhre ◽  
Bodil Roth ◽  
Sven Björkman
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
In Vitro Release ◽  
Sciatic Nerve Block ◽  
Depot Formulation ◽  
Duration Of Action ◽  
Depot Preparations

Background The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action. Methods The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations. Results The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects. Conclusions The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.

Pharmacodynamics and Pharmacokinetics of Lidocaine in a Rodent Model of Diabetic Neuropathy

2018 ◽  
Vol 128 (3) ◽  
pp. 609-619 ◽  
Author(s):  
Werner ten Hoope ◽  
Markus W. Hollmann ◽  
Kora de Bruin ◽  
Hein J. Verberne ◽  
Arie O. Verkerk ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Diabetic Neuropathy ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Nerve Fibers ◽  
Rodent Model ◽  
Sciatic Nerve Block ◽  
Zucker Diabetic Fatty Rats

Abstract Background Clinical and experimental data show that peripheral nerve blocks last longer in the presence of diabetic neuropathy. This may occur because diabetic nerve fibers are more sensitive to local anesthetics or because the local anesthetic concentration decreases more slowly in the diabetic nerve. The aim of this study was to investigate both hypotheses in a rodent model of neuropathy secondary to type 2 diabetes. Methods We performed a series of sciatic nerve block experiments in 25 Zucker Diabetic Fatty rats aged 20 weeks with a neuropathy component confirmed by neurophysiology and control rats. We determined in vivo the minimum local anesthetic dose of lidocaine for sciatic nerve block. To investigate the pharmacokinetic hypothesis, we determined concentrations of radiolabeled (14C) lidocaine up to 90 min after administration. Last, dorsal root ganglia were excised for patch clamp measurements of sodium channel activity. Results First, in vivo minimum local anesthetic dose of lidocaine for sciatic nerve motor block was significantly lower in diabetic (0.9%) as compared to control rats (1.4%). Second, at 60 min after nerve block, intraneural lidocaine was higher in the diabetic animals. Third, single cell measurements showed a lower inhibitory concentration of lidocaine for blocking sodium currents in neuropathic as compared to control neurons. Conclusions We demonstrate increased sensitivity of the diabetic neuropathic nerve toward local anesthetics, and prolonged residence time of local anesthetics in the diabetic neuropathic nerve. In this rodent model of neuropathy, both pharmacodynamic and pharmacokinetic mechanisms contribute to prolonged nerve block duration.

The Local Anesthetic Properties and Toxicity of Saxitonin Homologues for Rat Sciatic Nerve Block In Vivo

2000 ◽  
Vol 25 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Daniel S. Kohane ◽  
Nu T. Lu ◽  
Arman C. Gökgöl-Kline ◽  
Maria Shubina ◽  
Yu Kuang ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Sciatic Nerve Block ◽  
Rat Sciatic Nerve

scholarly journals Late hyaluronidase injection in local anesthesia: Morphofunctional evaluation in rat sciatic nerve block

2019 ◽  
Vol 30 (5) ◽  
pp. 692
Author(s):  
MariaAparecida Borsatti ◽  
AnnaCarolina Ratto Tempestini-Horliana ◽  
MarceloLazzaron Lamers ◽  
Maurício Yonamine ◽  
PatriciaVerónica Aulestia-Viera ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Local Anesthesia ◽  
Nerve Block ◽  
Sciatic Nerve Block ◽  
Rat Sciatic Nerve

The local anesthetic properties and toxicity of saxitonin homologues for rat sciatic nerve block in vivo

2000 ◽  
Vol 25 (1) ◽  
pp. 52-59 ◽  
Author(s):  
D KOHANE ◽  
N LU ◽  
A GOKGOLKLINE ◽  
M SHUBINA ◽  
Y KUANG ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Sciatic Nerve Block ◽  
Rat Sciatic Nerve

scholarly journals Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes

2015 ◽  
Vol 112 (51) ◽  
pp. 15719-15724 ◽  
Author(s):  
Alina Y. Rwei ◽  
Jung-Jae Lee ◽  
Changyou Zhan ◽  
Qian Liu ◽  
Meryem T. Ok ◽  
...  
Keyword(s):  
Cell Culture ◽  
Sciatic Nerve ◽  
Local Anesthesia ◽  
Nerve Block ◽  
Near Infrared ◽  
Tissue Reaction ◽  
On Demand ◽  
Nir Light

Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties. They were made photo-labile by encapsulation of a NIR-triggerable photosensitizer; irradiation at 730 nm led to peroxidation of liposomal lipids, allowing drug release. In vitro, 5.6% of TTX was released upon NIR irradiation, which could be repeated a second time. The formulations were not cytotoxic in cell culture. In vivo, injection of liposomes containing TTX and the photosensitizer caused an initial nerve block lasting 13.5 ± 3.1 h. Additional periods of nerve block could be induced by irradiation at 730 nm. The timing, intensity, and duration of nerve blockade could be controlled by adjusting the timing, irradiance, and duration of irradiation. Tissue reaction to this formulation and the associated irradiation was benign.

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