Article
Biology
Joseph L. Ransdell, Jonathan D. Moreno, Druv Bhagavan, Jonathan R. Silva, Jeanne M. Nerbonne
Summary: The resurgent component of the voltage-gated sodium current (I-NaR) is a depolarizing conductance that regulates the firing properties of various neuronal cell types. The mechanism behind the generation of I-NaR, mediated by voltage-gated sodium channels, remains unclear. This study provides evidence that resurgent Na+ influx occurs as a result of fast inactivating Nav channels transitioning into an open/conducting state on membrane hyperpolarization, and the decay of I-NaR reflects the slow accumulation of recovered/opened Nav channels into a second inactivated state. The amplitude of I-NaR can be modulated by factors such as the accessory Nav beta 4 channel subunit.
Review
Pharmacology & Pharmacy
Yiguo Zhang, Yixin Jing, Rui Pan, Ke Ding, Rong Chen, Qingtao Meng
Summary: Local anesthetics play a crucial role in perioperative analgesia for cancer patients, as they have been shown to reduce tumor recurrence and proliferation through various mechanisms. Clinical evidence and randomized trial data support the inhibitory effect of local anesthetics on tumor progression.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Masakazu Kotoda, Toru Matsuoka, Keiichi Wada, Selwyn Jayakar, Hirofumi Ino, Koji Kawago, Yasutomo Kumakura
Summary: This study investigated the potential of amiodarone, a multiple channel blocker, as a long-lasting local anesthetic and analgesic. It was found that amiodarone produced robust anesthesia and the co-administration of TRPV1 agonist capsaicin prolonged the duration of sensory blockade without affecting motor blockade. Low-dose amiodarone was also effective in relieving inflammatory pain without the need for capsaicin co-administration. Furthermore, local amiodarone did not cause any cardiovascular or central nervous system side effects.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Jannis Koerner, Simone Albani, Vishal Sudha Bhagavath Eswaran, Anna B. Roehl, Giulia Rossetti, Angelika Lampert
Summary: This article reviews the interaction between local anesthetics and voltage-gated sodium channels, discussing their mechanisms, effects, and specificity, and provides new perspectives for research.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sara Sixt, Michael Gruber, Gesche Kolle, Thies Galla, Diane Bitzinger
Summary: This study investigates the effect of selected local anesthetics (LAs) on polymorphonuclear neutrophils (PMNs), comparing a new isolation method with conventional ones. The results show that LAs can inhibit the chemotaxis and ROS production of PMNs, as well as impact NETosis and antigen expression. Additionally, different isolation methods also affect the survival time and migration duration of PMNs.
Article
Medicine, Research & Experimental
Wandi Zhu, Wei Wang, Paweorn Angsutararux, Rebecca L. Mellor, Lori L. Isom, Jeanne M. Nerbonne, Jonathan R. Silva
Summary: The study found that the accessory Na-V beta 1 and Na-V beta 3 subunits have different effects on the antiarrhythmic drugs lidocaine and ranolazine on Na(V)1.5 channel; recordings from mouse ventricular myocytes showed that loss of Scn1b affects the potencies of lidocaine and ranolazine differently; in vivo experiments suggested that Na-V beta 1 modulated drug responses at the whole-heart level.
Article
Biochemistry & Molecular Biology
Yan Wang, Mingfeng Qin, Junde Hou, Yongxue Chen
Summary: The study focused on the development of lidocaine-hybrid lipid-polymer nanoparticles (LDC@LPHNs) for long-acting local anesthetics, demonstrating their larger size, slow drug release, improved stability, and reduced cytotoxicity. In vivo examination showed that LDC@LPHNs exhibited significant and prolonged analgesic effects.
PROCESS BIOCHEMISTRY
(2021)
Review
Medicine, General & Internal
David Vinyes, Montserrat Munoz-Sellart, Lorenz Fischer
Summary: The use of low-dose local anesthetics (LAs) has shown positive effects in pain relief and clinical symptom management, improving patients' quality of life. However, further rigorous research is necessary to substantiate these effects.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Chemistry, Physical
Yan Li, Erxian Zhao, Li Li, Liying Bai, Wei Zhang
Summary: This study developed a modified release system using PVP-THB hydrogel to improve the pharmacological properties of the local anesthetic lidocaine. Mechanical properties and release profiles were investigated, showing slower release of associated LDC and prolonged anesthetic effect in vitro and in animal models. The new formulation of PVP-THB/LDC has potential applications in gradual release of local anesthetics.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Biochemistry & Molecular Biology
Lei Zhang, Xueqi Wang, Jingxin Chen, Shaohu Sheng, Thomas R. Kleyman
Summary: Using crosslinking and voltage clamp techniques, we identified specific intersubunit contacts in ENaC that modulate channel activity. Crosslinking between specific residues in the palm and thumb domains of different subunits activated or inhibited ENaC activity. These findings suggest the presence of microswitches at specific subunit interfaces that play a role in ENaC gating and regulation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Medicine, General & Internal
Entaz Bahar, Hyonok Yoon
Summary: Local anesthetics, especially lidocaine, are commonly used in dentistry with low risk of adverse allergic responses, but the reactions can range from moderate to life-threatening, requiring prompt diagnosis and treatment. This article reviews information on local anesthetics, their adverse reactions, causes, and management.
MEDICINA-LITHUANIA
(2021)
Review
Chemistry, Medicinal
Qi Wang, Yujun Zhang, Jin Liu, Wensheng Zhang
Summary: Local anesthetics provide complete analgesia with fewer side effects compared to systemic analgesics, but their clinical use is limited by their short duration of action. Therefore, local anesthetics with fast onset, long duration, selective nociceptive block, and low toxicity are highly desirable. Quaternary lidocaine derivatives (QLDs) have shown these characteristics in past electrophysiological studies.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Multidisciplinary Sciences
Yichen Liu, Carlos A. Z. Bassetto, Bernardo I. Pinto, Francisco Bezanilla
Summary: In this study, authors have reinterpreted the mechanism of fast inactivation in eukaryotic Na+ channels based on structural analysis and current measurements. They found that the final inactivation gate in Nav1.4 channel is comprised of two hydrophobic rings that close downstream of IFM binding. This alternative molecular framework provides a new understanding of fast inactivation.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Caihui Zhang, Cuiyu Xie, Yao Lu
Summary: Local anesthetic lidocaine can directly inhibit cancer cell proliferation and induce apoptosis, as well as indirectly influence immune regulation, anti-inflammation, and pain relief, showing potential clinical benefits in cancer treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Gali Garmi, Mark Parasol, Noah Zafran, Michael Rudin, Shabtai Romano, Raed Salim
Summary: This study suggests that single wound infiltration with bupivacaine and adrenaline during cesarean delivery can reduce postoperative pain, decrease opioid use, and potentially improve maternal satisfaction with pain management.