Novel Arylpiperazine Derivatives of Salicylamide with α1-Adrenolytic Properties Showed Antiarrhythmic and Hypotensive Properties in Rats

Figures

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  Figure 1. The therapeutic antiarrhythmic activity of the studied compounds in the adrenaline-induced arrhythmia model in rats. After an intravenous (iv) injection of adrenaline (20 µg/kg), the tested compounds were immediately administered iv. The control group received no additional treatment. The electrocardiogram (ECG) was recorded for the first 2 min and then at the 5th, 10th, and 15th min of the experiment. The criterion of antiarrhythmic activity was the decrease in or complete absence of extrasystoles in the ECG recording compared with the control group. The results are presented as means ± SD for active or maximum tested doses (1 mg/kg for JJGW01, JJGW07, and JJGW11, and 5 mg/kg for JJGW02, JJGW03, and JJGW12). Statistical analysis: one-way ANOVA (Dunnett’s post hoc); * p < 0.05, ** p < 0.01, *** p < 0.001; n = 5–6 rats.

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  Figure 2. The effect of arylpiperazine derivatives on the blood pressure response to methoxamine in rats. Pressor response to methoxamine (150 μg/kg) was estimated before and 5 min after the intravenous (iv) administration of the studied compounds at the lowest hypotensive doses (JJGW01 1mg/kg, JJGW02 2.5 mg/kg, JJGW03 5 mg/kg, JJGW07 5 mg/kg, JJGW11 2.5 mg/kg, JJGW12 5 mg/kg). The results are presented as means ± SD. Statistical analysis: paired t-test; ** p < 0.01, *** p < 0.001, **** p < 0.0001; n = 6 rats.

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  Figure 3. The experimental setup for studying prophylactic (Panel A) and therapeutic (Panel B) antiarrhythmic activity in rat models of arrhythmia, as well as the influence on electrocardiogram (ECG)_ parameters (Panel C). Adrenaline (20 μg/kg), calcium chloride (140 mg/kg), or aconitine (20 μg/kg) were used as arrhythmogens. All the compounds were administered intravenously (iv). The ECG observation was during the first 2 min and in the 5th, 10th, and 15th min.

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  Figure 4. The experimental setup for studying the influence of the tested compounds on blood pressure (Panel A), and the pressor response to methoxamine (Panel B) in normotensive rats. All the compounds were administered intravenously (iv). ME—methoxamine (150 µg/kg), BP—blood pressure.