Comparative study of antiarrhythmic and anti-ischemic activity of various salts of n1-(2,3,4-trimethoxybenzyl)-n2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethane-diamine

Introduction. As a screening result in a number of alkoxyphenyltriazoalkanes, the compound ALM-802, which in the form of its trihydrochloride has pronounced antiarrhythmic and antiischemic activity, was identified at the Federal State Budgetary Scientific Institution «Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies». However, the pH of the aqueous solution of this salt is quite low – 3.5, – which does not exclude the possibility of some local irritant activity in injectable dosage forms of the compound. Therefore, the succinate and citrate of compound ALM-802 – ALM-802S and ALM-802C, respectively, – were synthesized. The pH of the aqueous solutions of these compounds is significantly closer to neutral (ALM-802S – 5.8 and ALM-802C – 5.55), which does not suggest their local irritant activity, suggesting no local irritancy.

Objective. To study in a comparative aspect acute toxicity with a 24-hour observation period, antiarrhythmic and anti-ischemic activity of compounds ALM-802T, ALM-802S and ALM-802S.

Materials and methods. The toxicity parameters were determined on white outbred male mice, the calculation was carried out according to Finney. The antiarrhythmic activity of the compounds (2 mg/kg) was studied on a model of aconitine cardiac arrhythmias in male white rats. The anti-ischemic effect of the substances was tested on a model of acute subendocardial ischemia caused by the nonselective beta-adrenomimetic isoproterenol (20 mg/kg/min for 5 minutes). The intensity of ischemic damage was judged by the magnitude of ST segment depression on the ECG (standard lead II) 5 minutes after the start of the isoproterenol infusion.

Results. Analysis of the data obtained showed that the LD50/24 of the studied ALM-802 salts are comparable, they belong to the IV class of toxicity – low-toxic compounds. They are equally highly effective in models of aconitine heart rhythm disorders and subendocardial ischemia.

Conclusion. The ALM-802T, ALM-802S and ALM-802S compounds on the studied models do not differ in efficiency.

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