Baseline Response, Monitoring, and Cross-Resistance of Spodoptera frugiperda (Lepidoptera: Noctuidae) to Sodium Channel Blocker Insecticides in Brazil

2021 ◽  
Author(s):  
Ingrid S Kaiser ◽  
Rubens H Kanno ◽  
Anderson Bolzan ◽  
Fernando S A Amaral ◽  
Ewerton C Lira ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Spodoptera Frugiperda ◽  
Channel Blocker ◽  
Resistance Management ◽  
Response Monitoring ◽  
Cross Resistance ◽  
Channel Blockers ◽  
Sodium Channel Blocker ◽  
Baseline Response ◽  
Lepidoptera Noctuidae

Abstract Spodoptera frugiperda (J.E. Smith) is one of the key cross-crop pests in Brazilian agroecosystems. Field-evolved resistance of S. frugiperda to some conventional insecticides and Bt proteins has already been reported. Thus, the use of insecticides with new mode of action such as sodium channel blockers (indoxacarb and metaflumizone) could be an important tool in insecticide resistance management (IRM) programs. To implement a proactive IRM, we conducted baseline response and monitoring to indoxacarb and metaflumizone in 87 field populations of S. frugiperda collected from major maize-growing regions of Brazil from 2017 to 2020, estimated the frequency of resistance alleles to indoxacarb, and evaluated cross-resistance of indoxacarb and metaflumizone to some selected insecticides and Bt proteins. Low variation in susceptibility to indoxacarb (4.6-fold) and metaflumizone (2.6-fold) was detected in populations of S. frugiperda in 2017. The frequency of the resistance allele to indoxacarb was 0.0452 (0.0382–0.0527 CI 95%), by using F2 screen method. The mean survival at diagnostic concentration, based on CL99, varied from 0.2 to 12.2% for indoxacarb and from 0.0 to 12.7% for metaflumizone, confirming high susceptibility of S. frugiperda to these insecticides in Brazil. No cross-resistance was detected between sodium channel blocker insecticides and other insecticides (organophosphate, pyrethroid, benzoylurea, spinosyn, and diamide) and Bt proteins. These findings showed that sodium channel blocker insecticides are important candidates to be exploited in IRM strategies of S. frugiperda in Brazil.

Resistance Risk Evaluated by Metaflumizone Selection and the Effects on Toxicities Over Other Insecticides in Spodoptera exigua (Lepidoptera: Noctuidae)

2019 ◽  
Vol 112 (5) ◽  
pp. 2354-2361
Author(s):  
Xing-Xing Sun ◽  
Hong-Yang Li ◽  
Ying-Jie Jiang ◽  
Jun-Xi Zhang ◽  
Hui-Ling Gu ◽  
...  
Keyword(s):  
Spodoptera Exigua ◽  
Channel Blocker ◽  
Resistance Management ◽  
Cross Resistance ◽  
Realized Heritability ◽  
Sodium Channel Blocker ◽  
Resistance Risk ◽  
Resistance Evolution ◽  
Threshold Trait ◽  
Lepidoptera Noctuidae

Abstract Metaflumizone is a novel semicarbazone insecticide. It functions as a sodium channel blocker insecticide (SCBI) with excellent insecticidal activity on most economically important lepidopterous pests. This study assessed the resistance risk of Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae) to metaflumizone in the laboratory and the effects of metaflumizone selection on toxicities to other insecticides. Spodoptera exigua collected from a field population at Huizhou in 2012 were successively challenged by metaflumizone to evaluate the risk of resistance evolution. Twelve generations of selection increased resistance to metaflumizone by 3.4-fold and threshold trait analysis revealed that the realized heritability (h2) of this resistance was 0.086. When h2 was equal to 0.086 and 90% of individuals were killed at each generation, LC50 to metaflumizone increased by 10-fold after 15 generations. The selection by metaflumizone did not increase the resistance to indoxacarb, chlorantraniliprole, spinosad, methomyl, or endosulfan, suggesting a lack of cross-resistance. However, metaflumizone challenge upheld the recession of resistance to emamectin benzoate, chlorfluazuron, and tebufenozide. The block of resistance drops by metaflumizone exposure implied a possible cross-resistance between metaflumizone and these three insecticides. These results contribute to integrated resistance management of S. exigua.

Voltage Gated Sodium Channel Blockers: Synthesis of Mexiletine Analogues and Homologues

2020 ◽  
Vol 27 ◽  
Author(s):  
Alessia Catalano ◽  
Carlo Franchini ◽  
Alessia Carocci
Keyword(s):  
Sodium Channel ◽  
Channel Blocker ◽  
Parent Compound ◽  
Channel Blockers ◽  
Sodium Channel Blocker ◽  
Starting Point ◽  
Channel Blocking ◽  
Blocking Activity ◽  
Synthetic Routes ◽  
Lateral Sclerosis

: Mexiletine is an antiarrhythmic drug belonging to IB class, acting as sodium channel blocker. Besides its well-known activity on arrhythmias, its usefulness in the treatment of myotonia, myotonic distrophy and amyotrophic lateral sclerosis is now widely recognized. Nevertheless, it has been retired from the market in several countries because of its undesired effects. Thus, several papers were reported in the last years about analogues and homologues of mexiletine being endowed with a wider therapeutic ratio and a more selectivity of action. Some of them showed sodium channel blocking activity higher than the parent compound. It is noteworthy that mexiletine is used in therapy as a racemate even though a difference in the activities of the two enantiomers were widely demonstrated, with (–)-(R)-enantiomer being more active: this finding led several research groups to study mexiletine and its analogues and homologues in their optically active forms. This review summarizes the different synthetic routes used to obtain these compounds. They could represent an interesting starting point to new mexiletine-like compounds without common side effects related to the use of mexiletine.

Vanilloid Receptor Agonists Potentiate the In Vivo Local Anesthetic Activity of Percutaneously Injected Site 1 Sodium Channel Blockers 

1999 ◽  
Vol 90 (2) ◽  
pp. 524-534 ◽  
Author(s):  
Daniel S. Kohane ◽  
Yu Kuang ◽  
Nu T. Lu ◽  
Robert Langer ◽  
Gary R. Strichartz ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Channel Blocker ◽  
Synergistic Effects ◽  
Small Diameter ◽  
Channel Blockers ◽  
Sodium Channel Blocker ◽  
Sodium Channel Blockers ◽  
Nerve Blockade ◽  
Motor Strength

Background Capsaicin, the pungent ingredient in chili peppers, is a vanilloid with noxious and analgesic effects that inhibits tetrodotoxin-resistant sodium currents. Because tetrodotoxin-resistant currents are found primarily in small-diameter nociceptor afferents of the peripheral nerves, their inhibition may lead to selective analgesia. Therefore, the authors evaluated the interactions between tetrodotoxin, a site 1 sodium channel blocker, and capsaicin on nerve blockade in vivo. Methods Percutaneous sciatic nerve injections with 0 to 9.9 mM capsaicin, 0 to 120 microM tetrodotoxin, or both were administered to male Sprague-Dawley rats. Thermal nociceptive and motor blockade were measured. Data were expressed as medians with 25th and 75th percentiles. Results Capsaicin produced a transient increase in thermal latency with no effect on motor strength. Tetrodotoxin reduced motor strength for a longer duration than nociception. The interaction between tetrodotoxin and capsaicin was synergistic, as evidenced by (1) supraadditive prolongation of both nociceptive and motor block, with the effect of capsaicin reversed by the vanilloid antagonist capsazepine, and (2) synergism in the frequency that rats achieved maximal block shown by isobolographic analysis. The combination of tetrodotoxin and capsaicin showed less motor predominance than tetrodotoxin did alone. Similar interactions were found between tetrodotoxin and resiniferatoxin (another vanilloid), and between capsaicin and saxitoxin (another site 1 sodium channel blocker), but much less so between bupivacaine and capsaicin. Conclusions Site 1 sodium channel blockers and vanilloids have synergistic effects on nerve blockade in vivo. These interactions may be useful in developing prolonged local anesthetics and elucidating mechanisms of functionally selective nerve blockade.

scholarly journals Rate-dependent effects of lidocaine on cardiac dynamics: Development and analysis of a low-dimensional drug-channel interaction model

2021 ◽  
Vol 17 (6) ◽  
pp. e1009145
Author(s):  
Steffen S. Docken ◽  
Colleen E. Clancy ◽  
Timothy J. Lewis
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Channel Blocker ◽  
Interaction Model ◽  
Drug Binding ◽  
Channel Blockers ◽  
Sodium Channel Blocker ◽  
Channel Interaction ◽  
Rate Dependent ◽  
Low Dimensional

State-dependent sodium channel blockers are often prescribed to treat cardiac arrhythmias, but many sodium channel blockers are known to have pro-arrhythmic side effects. While the anti and proarrhythmic potential of a sodium channel blocker is thought to depend on the characteristics of its rate-dependent block, the mechanisms linking these two attributes are unclear. Furthermore, how specific properties of rate-dependent block arise from the binding kinetics of a particular drug is poorly understood. Here, we examine the rate-dependent effects of the sodium channel blocker lidocaine by constructing and analyzing a novel drug-channel interaction model. First, we identify the predominant mode of lidocaine binding in a 24 variable Markov model for lidocaine-sodium channel interaction by Moreno et al. Specifically, we find that (1) the vast majority of lidocaine bound to sodium channels is in the neutral form, i.e., the binding of charged lidocaine to sodium channels is negligible, and (2) neutral lidocaine binds almost exclusively to inactivated channels and, upon binding, immobilizes channels in the inactivated state. We then develop a novel 3-variable lidocaine-sodium channel interaction model that incorporates only the predominant mode of drug binding. Our low-dimensional model replicates an extensive amount of the voltage-clamp data used to parameterize the Moreno et al. model. Furthermore, the effects of lidocaine on action potential upstroke velocity and conduction velocity in our model are similar to those predicted by the Moreno et al. model. By exploiting the low-dimensionality of our model, we derive an algebraic expression for level of rate-dependent block as a function of pacing frequency, restitution properties, diastolic and plateau potentials, and drug binding rate constants. Our model predicts that the level of rate-dependent block is sensitive to alterations in restitution properties and increases in diastolic potential, but it is insensitive to variations in the shape of the action potential waveform and lidocaine binding rates.

scholarly journals Inhibiting cough by silencing large pore-expressing airway sensory neurons with a charged sodium channel blocker

2020 ◽  
Author(s):  
Ivan Tochitsky ◽  
Sooyeon Jo ◽  
Nicholas Andrews ◽  
Masakazu Kotoda ◽  
Benjamin Doyle ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sensory Neurons ◽  
Channel Blocker ◽  
Allergic Inflammation ◽  
Selective Inhibition ◽  
Channel Blockers ◽  
Common Condition ◽  
Sodium Channel Blocker ◽  
Large Pore ◽  
Extracellular Activity

Although multiple diseases of the respiratory system cause cough, there are few effective treatments for this common condition. We previously developed a strategy to treat pain and itch via the long-lasting inhibition of nociceptor sensory neurons with QX-314, a cationic sodium channel blocker that selectively enters only into activated nociceptors by permeating through the endogenous TRPV1 and TRPA1 large pore ion channels they express. In this study we design and characterize BW-031, a novel cationic compound with ~6-fold greater potency than QX-314 for inhibiting sodium channels when introduced inside cells and with minimal extracellular activity. We show that inhalation of aerosolized BW-031 effectively inhibits citric acid-induced cough in an allergic inflammation guinea pig cough model. These data support the use of charged sodium channel blockers for the selective inhibition of airway sensory neurons with activated large pore channels as a novel targeted therapy for treating cough.

scholarly journals B-PO04-024 PREDICTION OF A POSITIVE SODIUM CHANNEL BLOCKER PROVOCATION TEST IN PATIENTS SUSPECTED OF BRUGADA SYNDROME

Heart Rhythm ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. S289
Author(s):  
Martijn Hendrik van der Ree ◽  
Jeroen Vendrik ◽  
Tom E. Verstraelen ◽  
Jan A. Kors ◽  
Ahmad S. Amin ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Brugada Syndrome ◽  
Channel Blocker ◽  
Provocation Test ◽  
Sodium Channel Blocker

scholarly journals From Plastic-Bottle-Toxin to Sodium Channel Blocker: A New Role for Bisphenol A

2010 ◽  
Vol 98 (3) ◽  
pp. 114a
Author(s):  
Angelika Lampert ◽  
Andrias O. O'Reilly ◽  
B.A. Wallace ◽  
Christian Alzheimer
Keyword(s):  
Bisphenol A ◽  
Sodium Channel ◽  
Channel Blocker ◽  
Sodium Channel Blocker ◽  
Plastic Bottle

Synthesis of Vixotrigine, a Use-Dependent Sodium Channel Blocker. Part 1: Development of Bulk Supply Routes to Enable Proof of Concept

2020 ◽  
Vol 24 (12) ◽  
pp. 2802-2813 ◽  
Author(s):  
Gerard Giblin ◽  
Adrian Heseltine ◽  
William Kiesman ◽  
David MacPherson ◽  
James Ramsden ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Channel Blocker ◽  
Proof Of Concept ◽  
Sodium Channel Blocker
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