Poster presentation
329
STUDY OF ANTIARRHYTHMIC ACTIVITY OF MODIFIED
FORMS OF AMIODARON
V.V. Uzbekov
1
, I.Z. Jumayev
2
, Sh.Yu. Rustamov
2
, Yu.I. Oshchepkova
1*
,
P.B. Usmanov
2
, Sh.I. Salikhov
1
1) A.S. Sadykov Institute of Bioorganic Chemistry Academy of Sciences of the Republic
of Uzbekistan, *
e-mail: joshepkova05@rambler.ru
2) Institute of Biophysics and Biochemistry National University of Uzbekistan
Heart rhythm disturbances are one of the most complex and urgent problems of
modern cardiology. Arrhythmias are detected both in various cardiovascular diseases
and in healthy individuals. The spectrum of clinical
manifestations of cardiac
arrhythmias varies from asymptomatic to severe course, from prognostically
insignificant arrhythmias to determining the nature of the long-term outcome.
Amiodarone is the most effective of the existing antiarrhythmic drugs. It is even called
"arrhythmolytic drug". Along with all the advantages,
the main disadvantage of
amiodarone is the likelihood of developing many extracardiac side effects, which are
observed in 10-52% of patients with long-term use of the drug.
The aim of this work is to study the antiarrhythmic and inotropic activity of
complexes of amiodarone hydrochloride (AmdHC) with glycyrrhizic acid (GA) and its
monoammonium salt (MASGA) in models of CaCl
2
-induced arrhythmia in comparison
with АmdHC.
The study in experiments on the papillary muscle of the rat heart was carried out on
the complexes of GA-AmdHC (2:1), GA-AmdHC (4:1), GA-AmdHC (8:1), MASGA-
AmdHC (2:1), MASGA-AmdHC (4:1) and MASGA-AmdHC (8:1).
It was determined
that in the presence of complexes GA-AmdHC (2:1) (5-100 μM), GA-AmdHC (4:1) (5-
60 μM), GA-AmdHC (8:1) (5-40 µM), MASGA-AmdHC (2:1) (5-120 µM), MASGA-
AmdHC (4:1) (5-100 µM) and MASGA-AmdHC (8:1) (5-30 µM) the papillary muscle
contraction force decreases to 12.3±5.5%, 16.4±3.9%, 6.2±3.4%, 4.3±3.5%, 3.8±3.5 %
and 2.7±2.4%, respectively, from the control level. Based on the conducted studies, it
can be assumed that GA-AmdHC (8:1) and MASGA-AmdHC (8:1) have a stronger
negative inotropic effect than amiodarone and other complexes. When studying the
effects of complex compounds on the CaCl
2
-induced
arrhythmia model, it was found
that their addition during the second phase of CaCl
2
action leads to the restoration of
papillary muscle contractions in response to stimulation.
In control experiments with
amiodarone, it was found that, in its presence, the restoration of muscle contractions
occurs 10 min after its introduction into the incubation medium. In the presence of GA-
AmdHC (8:1), the restoration of muscle contractions occurred within 7 minutes after its
introduction into the incubation medium. A more pronounced effect on the background
of CaCl
2
-induced arrhythmia has MASGA-AmdHC (8:1), in the presence of which the
restoration of muscle contractions was observed within 3 minutes after its introduction
into the incubation medium. The data obtained indicate that
the modification of the
structure of AmdHC by the introduction of MASGA provides the complex MASGA-
AmdHC (8:1) with a higher negative inotropic and antiarrhythmic activity. Such an
increase in the inotropic and antiarrhythmic activity of the MASGA-AmdHC (8:1)
complex may be due to the presence of additional MASGA groups in its structure,
which can
increase its lipophilicity and, accordingly, membrane activity.