Combination Formulation of Tetrodotoxin and Lidocaine as a Potential Therapy for Severe Arrhythmias.
Mar Drugs
; 17(12)2019 Dec 05.
Article
in En
| MEDLINE
| ID: mdl-31817438
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arrhythmias, Cardiac
/
Tetrodotoxin
/
Lidocaine
/
Anti-Arrhythmia Agents
Limits:
Animals
Language:
En
Journal:
Mar Drugs
Journal subject:
BIOLOGIA
/
FARMACOLOGIA
Year:
2019
Type:
Article
Affiliation country:
China