Current concepts of the mechanism of action of local anesthetics. Strichartz G R Journal of dental research Recent experiments are reviewed to present a current view of the mechanisms of conduction block by local anesthetics. Local anesthetics block the sodium channels whose opening causes the rising phase of the action potential. Both charged and neutral forms of local anesthetics are able to block channels. Charged anesthetics interfere with a "gating" mechanism after gaining access to a "receptor" site in the aqueous pore of the channel from the axoplasmic surface of the membrane. This site is only available to charged compounds when the gate of the channel is open. In contrast, uncharged compounds (including the free base form of local anesthetics) appear to reach the site through the membrane's lipid interior, bypassing the channel "gates." Anesthetics blocking the gate of the channel can either enhance or inhibit the normal inactivation mechanism of the sodium channel, depending on the particular anesthetic. 10.1177/00220345810600080904

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants. The Journal of general physiology Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. 10.1085/jgp.201611668

In vitro antibacterial effects of topical local anesthetics. Sedef Gocmen J,Buyukkocak Unase,Caglayan Osman,Aksoy Altan The Journal of dermatological treatment BACKGROUND:The antibacterial activities of local anesthetics are recognized. OBJECTIVE:To investigate in vitro the activity of topical local anesthetic ointments at clinical doses. METHODS:The activity of two different local anesthetic ointments including lidocaine 5% and lidocaine/prilocaine 2.5% was tested against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Streptococcus pyogenes and Enterococcus faecalis by the disc-diffusion method. Sterile discs containing topical local anesthetic drugs were prepared taking into account the doses of ointments used in clinical practice. The validity of the methodology was confirmed using topical antibacterial mupirocin. The inhibition zones of the discs were measured. RESULTS:Mupirocin inhibited all the bacteria. Both local anesthetic ointments were found to be most effective on E. coli, whereas they had no effects on P. aeruginosa. Lidocaine 5% revealed antibacterial activity against S. aureus, S. epidermidis, E. coli, S. pyogenes and E. faecalis, but lidocaine/prilocaine 2.5% showed no activity on E. faecalis and inhibited S. pyogenes only at double doses. It was also observed that the antibacterial activity was in a dose-dependent manner. CONCLUSION:In the light of these findings, it might be concluded that topical local anesthetic ointments in routine settings may have a preventive role against some bacteria. 10.1080/09546630802050498

A review and new insights to antimicrobial action of local anesthetics. Razavi Bibi Marjan,Fazly Bazzaz Bibi Sedigheh European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology Local anesthetics (LAs) are medications which can provide analgesia in distinct body regions through the blockade of voltage-gated sodium channels. Besides pain management, the supplemental role of LAs as antimicrobial agents has been documented in several studies. Different databases including PubMed, Scopus, and Web of Science with the name of different local anesthetics and related names for antimicrobial keywords were searched without time limitation. This review summarized different in vitro and in vivo studies regarding antimicrobial effects of different LAs with focuses on antimicrobial applications of most studied LAs, interaction with different agents which combined with LAs, and mechanisms of action and structural dependence of LAs antibacterial effects. Among different LAs, lidocaine is the most studied preparation. Reduction of the incidence of endophthalmitis after intravitreal injection, prophylaxis for surgical wound infections, prevention of the incidence of catheter-associated infections, oral biofilm reduction on the buccal mucosa, and prevention against bacteria that produced nosocomial infection are some examples of lidocaine antimicrobial application. Studies showed that different factors including structure, concentration, duration of exposure, type of microorganism tested, and temperature affect the degree of LA antimicrobial activity. In addition, various agents such as antibiotics, preservatives, opioids, epinephrine, and propofol can combine with LAs and affect their antimicrobial properties through synergistic or antagonistic action. Due to antibacterial activities, LAs could be applied in a clinic for prophylaxis of surgical site infection. In the application of LAs prior to diagnostic procedures caution should be needed; otherwise, when culturing the specimen, they could lead to false negative results. 10.1007/s10096-018-03460-4

Antimicrobial Properties on Non-Antibiotic Drugs in the Era of Increased Bacterial Resistance. Lagadinou Maria,Onisor Maria Octavia,Rigas Athanasios,Musetescu Daniel-Vasile,Gkentzi Despoina,Assimakopoulos Stelios F,Panos George,Marangos Markos Antibiotics (Basel, Switzerland) In recent years, due to the dramatic increase in and global spread of bacterial resistance to a number of commonly used antibacterial agents, many studies have been directed at investigating drugs whose primary therapeutic purpose is not antimicrobial action. In an era where it is becoming increasingly difficult to find new antimicrobial drugs, it is important to understand these antimicrobial effects and their potential clinical implications. Numerous studies report the antibacterial activity of non-steroidal anti-inflammatory drugs, local anaesthetics, phenothiazines such as chlorpromazine, levomepromazine, promethazine, trifluoperazine, methdilazine and thioridazine, antidepressants, antiplatelets and statins. Several studies have explored a possible protective effect of statins inreducing the morbidity and mortality of many infectious diseases. Various non-antibiotic agents exhibit antimicrobial activity via multiple and different mechanisms of action. Further studies are required in the field to further investigate these antimicrobial properties in different populations. This is of paramount importance in the antimicrobial resistance era, where clinicians have limited therapeutic options to combat problematic infections. 10.3390/antibiotics9030107