The study of the analeptic activity of derivatives of sulfur- and nitrogen-containing heterocycles on the model of thiopental narcosis

Abstract

The range of the use of analeptics covers a number of urgent states (shock, collapse, anesthesia, asphyxia, hypoxia, bacterial intoxication with chemical compounds or drugs suppressing the CNS functions), i.e. almost all areas of urgent therapy of peacetime, military medicine and disaster medicine. However, over the past 50 years, their arsenal has not only been renewed, but even reduced to 6 drugs. This is because of the lack of standardized methods for assessing analeptic efficacy and the theoretical basis for their development.

Aim. To search and study the promising substances with the analeptic effect among derivatives of sulfur- and nitrogen-containing heterocycles on the standardized model of thiopental narcosis.

Materials and methods. The results of the experiment conducted confirm the adequacy of the method tested, which allows to compare the effect of original substances and classical analeptics on the central nervous system (CNS) and respiratory center (RC) objectively qualitatively and quantitatively (statistically reliably) by intraperitoneal administration of optimal doses: anesthesia (sodium thiopental); at the peak of anesthesia the classical analeptic sulfocamphocaine (SCC) for the first group of animals, the test substances for the second and third groups with the subsequent observation of the anesthesia sleep duration, the dynamics of the frequency of respiratory movements, the psychomotor state and the physiological functions of mice in anesthesia and after awakening.

Results. It has been found that the optimal depth and duration of anesthesia is achieved by the intraperitoneal injection of 42 mg/kg of thiopental sodium. The most effective was the traditional analeptic SCC, which in the optimal dose (20 mg/kg) accelerated the awakening of animals by 35 %. Heterosides-21, -31 provided a reliable reduction in duration of anesthesia by 26.8 % and 24.4 % in the dose of 2 mg/kg. After introduction of the test substances the frequency of respiratory movements (RM) increased significantly (p < 0.05) for 10 min compared to the control group, reaching the maximum (85.3 DD/min) in the SCC group. It indicates its superiority in the rate of RC stimulation compared to both Heterosides, which with the concentration of 10 times less than SCC were statistically insignificantly inferior to it by 8.2 % and 10.6 %, respectively.

Conclusions. The model of thiopental narcosis makes it possible to statistically reliably compare the effectiveness of classical drugs and original substances by the signs of the awakening effect on the CNS and RC; it can be recommended as a reference model for the purposeful search of analeptics. On the example of studying heterosides the adequacy of the screening model proposed and the prospects of derivatives of sulfur- and nitrogen-containing heterocycles for the search of effective analeptics have been confirmed.