The standardized model of alcoholic anesthesia for the purposeful screening of analeptics
DOI:
https://doi.org/10.24959/cphj.17.1440Keywords:
alcohol, anesthesia, heterocide, analeptic, awakening effect, respiratory rate, respiratory centerAbstract
The analysis of pathogenetic mechanisms of development of urgent conditions (anesthesia, asphyxia, hypoxia, shock, collapse, bacterial intoxication, poisoning by chemical compounds or drugs suppressing the function of the central nervous system) suggests that among urgent therapies analeptic drugs (AD) are of a paramount importance. At the same time, their assortment has not only been updated in the last 50 years, but reduced to 6 drugs. This situation is conditioned by the absence of the standard for selecting AD.
Aim. To create a standard for selecting AD which can quantitatively (statistically reliable) evaluate both the level of the awakening effect in general and its mechanism (namely its analeptic action); compare and determine the priorities of further study of substances; create theoretical foundations for the purposeful search of AD and optimize the scientific research.
Materials and methods. During the research the procedure of AD selection was developed experimentally. It consists in intraperitoneal introduction of the narcotic agent (ethanol) in the optimal dose; introduction of a classical analeptic sulfocamphocaine (SCC) in the standard dose at the peak of anesthesia to one group of mice, while the second group received the substance studied (Heterocide-31) with the subsequent recording of the anesthesia duration, dynamics of the frequency of respiratory movements, assessment of the psychomotor state and physiological functions of animals during anesthesia and after awakening assuming that in the course of the experiment the specific dose-time conditions for introduction of substances are observed.
Results. The results of the study show that the maximum efficacy (18.2 %) was achieved by Heterocide-31 in the dose of 1 mg / kg, while the optimal dose of SCC (20 mg / kg) accelerated awakening of animals by 19.5 %. Thus, Heterocide-31 showed almost identical activity in the concentration of 20 times lower than SCC. The fact that after introduction of Heterocide-31 the respiratory rate (RR4) significantly increases (p <0.05) by 1.6 times already within the first minute compared to the control group, and the maximum (125) respiratory movements / min in the reference drug group is achieved only in 6 min (RR5) indicates the 6-fold advantage of Heterocide-31 by the rate of the respiratory center stimulation and allows referring the latter to a number of promising analeptics.
Conclusions. The model of pharmacological screening proposed accelerates the purposeful search of original AD, has a complete novelty, originality, easy in repeatability, economic, environmental and humanistic advantages, namely it reduces time and the number of laboratory animals, the cost of experiments, increases the information value of the experiments. The method has been tested on heterosides and suggests that derivatives of sulfur and nitrogen-containing heterocycles are promising for the search of original AD having a significant advantage over classical analeptics.
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