Organizing co mmittee

 
 

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Plenary presentation 
10 
ANTIARRHYTHMICS BASED ON DITERPENE ALKALOIDS.
CREATING AN INJECTION FORM 
M.S. Yunusov, E.M. Tsyrlina, S.P. Ivanov, T.M. Gabbasov, S.G. Yunusova 
 
Ufa Institute of Chemistry, UFRC RAS, Russian Federation, 
450054, Ufa, ave. October, 71, e-mail: [e-mail] 
The hydrobromic salt of lappaconitine by name "Allapinin" was introduced into 
medical practice as an antiarrhythmic agent in 1987. 
The drug allapinin was approved for use, both in tablet and ampoule (injection) form. 
However, intravenous use of the drug was not widely used due to the late onset of the 
therapeutic effect and adverse cardiac effects.
N-deacetyllappaconitine (DAL), the main 
metabolite of the drug allapinin, unlike the latter, realizes its antiarrhythmic effect in a 
significantly lower dose, is less toxic, surpasses allapinin in the speed of development of 
the antiarrhythmic effect. The most acceptable dosage form of DAL is the 
monohydrochloride of N-deacetylappaconitine (DAL•НСl). 
DAL•HCl, as well as allapinin, inhibits Na+ currents. Unlike allapinin, DAL•HCl 
also exhibits the properties of a K-channel inhibitor and, according to its 
electrophysiological characteristics, can be attributed to antiarrhythmics combining the 
properties of 1C and III classes according to the Vaugham-Williams classification. 
The concentrations of DAL•HCl, which effectively inhibit Na+ channels, are 
approximately 20 times less than those for allapinin.
These data seem to be quite 
important, since DAL•HCl is not only active in significantly lower concentrations, but 
also less toxic than allapinin, which suggests that in the case of its potential use in the 
clinic, the spectrum of side effects of DAL•HCl will be significantly less than that of 
allapinin. 
The study of the basicity of two DAL nitrogen atoms showed, that in the pH range 6-
7, the nitrogen atom of the piperidine ring is protonated, and in the range pH 2-3 the 
nitrogen of the aromatic group is protonated. Given the data obtained, it is obvious that 
the stable form, especially in aqueous solutions, can only be a mono-salt of DAL. The 
conditions for the analysis of DAL by HPLC have been developed. 
Thus, these data suggest that DAL can serve as a basis for obtaining a new effective 
antiarrhythmic agent in injectable form. 

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Plenary presentation
11