Combination Formulation of Tetrodotoxin and Lidocaine as a Potential Therapy for Severe Arrhythmias

Abstract

Severe arrhythmias—such as ventricular arrhythmias—can be fatal, but treatment options are limited. The effects of a combined formulation of tetrodotoxin (TTX) and lidocaine (LID) on severe arrhythmias were studied. Patch clamp recording data showed that the combination of LID and TTX had a stronger inhibitory effect on voltage-gated sodium channel 1.5 (Nav1.5) than that of either TTX or LID alone. LID + TTX formulations were prepared with optimal stability containing 1 μg of TTX, 5 mg of LID, 6 mg of mannitol, and 4 mg of dextran-40 and then freeze dried. This formulation significantly delayed the onset and shortened the duration of arrhythmia induced by aconitine in rats. Arrhythmia-originated death was avoided by the combined formulation, with a decrease in the mortality rate from 64% to 0%. The data also suggests that the anti-arrhythmic effect of the combination was greater than that of either TTX or LID alone. This paper offers new approaches to develop effective medications against arrhythmias.

Can bioactive peptides of Lagocephalus sceleratus be evaluated in the functional food industry

“…TTX was also reported as an analgesic for various pains and also cancer (Nieto et al, 2012). TTX combined with lidocaine is also proposed for severe arrhythmias by Hong et al (2019). From these publications, it could be inferred that bioactive pellets including bioactive peptides mentioned in this study can be exploited in these diseases.…”

“…The present paper reveals that there are many bioactive peptides and their BIOPEP parameters are in comparable levels with well-consumed B. taurus and G. gallus domesticus. Moreover, TTX have been recently associated with promising therapeutic effects (Nieto et al, 2012;Hong et al, 2018;Hong et al, 2019). Therefore, more wet lab-based studies are strongly recommended to exploit the idea on the utilization of widely distributed L. sceleratus in the Mediterranean Sea.…”

“…However, it must be noted that TTX should be removed from L. sceleratus based products for possible human consumption because of its toxic effects on human metabolism. Alternatively, TTX containing formulas like in Hong et al 2018 andHong et al 2019 may be prepared to evaluate the biomass of the species (for therapeutic purposes).…”

Attenuation and Structural Transformation of Crassicauline A During Sand Frying Process and Antiarrhythmic Effects of its Transformed Products

“…To further investigate the antiarrhythmic activity of the three converted alkaloids, the testing was performed in vivo in 233 rats. The rats were randomly divided into the following 15 groups, a minimum of ten animals were used in each group: the blank solvent group (Take 4 ml of 1% HCl-ethanol solution, dilute it with saline, add 5% NaOH to adjust pH 7, and fixed volume with saline to 100 ml), the control group (Aconitine, 0.03 mg/kg body weight), the positive control groups (Lidocaine, 5.0 mg/kg ( Hong et al, 2019 ) body weight; propafenone, 3.2 mg/kg ( Li et al, 2006 ) body weight), the compound 1 groups (0.05, 0.20, 0.40, and 0.60 mg/kg body weight), the compound 2 groups (0.05, 0.20, 0.30, and 0.40 mg/kg body weight), and the compound 4 groups (0.05, 0.20, and 0.40 mg/kg body weight). The preparation methods of aconitine, positive drugs, and the experimental compounds were the same as the blank solvent.…”

Wenxin Keli for the Treatment of Arrhythmia—Systems Pharmacology and In Vivo Pharmacological Assessment

“…It may remain asymptomatic or lead to other cardiovascular disorders, heart failure, stroke, and cardiac arrest. Severe arrhythmias, such as ventricular arrhythmias, have limited treatment options, causing them to be fatal ( Hong et al, 2019 ). Numerous ongoing studies have reported treatment solutions for arrhythmias ( Tian et al, 2019 ).…”