RU2362556C2 - APPLICATION OF HYDROBROMIDE 2-AMINO-4-ACETYLTHYAZOLE [5,4-b] INDOLE FOR WORKING CAPACITY INCREASE - Google Patents

Abstract

FIELD: medicine; pharmaceutics.

SUBSTANCE: application of hydrobromide 2-amino-4-acetylthyazole [5,4-b] indole of the formula

known before hepatoprotector and antihypoxic agent, for working capacity rising. Endurance rising in 1 hour per 2.34 times, in a day - in 1.76 times after unitary introduction of substance is shown.

EFFECT: activating also it is long remaining effect.

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Description

There is no doubt about the assertion that physical endurance is the most important indicator of the state of health and the body's adaptation to changing environmental conditions. A variety of harmful factors can contribute to the development of fatigue in humans in an emergency. Maintaining high physical performance under these circumstances is an essential condition for completing tasks and even saving lives.

Previously, hepatoprotective activity of 2-amino-4-acetylthiazolo [5,4-b] indole hydrobromide was established (RF Patent 2076867, MKI ³ 6 С07D 478/04, А61К 31/40), as well as antihypoxic with respect to hemic and hypercapnic hypoxia ( Pat. 2281095 RF, MKI ³ A61K 31/429, C07D 513/04, A61P 39/00).

It is known that substances with antihypoxic properties, for example, bemitil, can increase physical performance. We studied compound 1 for the detection of its actoprotective properties, which was not previously known.

The study of actoprotective activity began with a test of limiting swimming on white outbred mice of males weighing 16-22 g (in groups of 10 animals), which were injected intraperitoneally once tested compound in the form of a thin suspension in Tween-20 with a volume of 0.2 ml in doses of 10, 25 , 50 mg / kg, the control received an injection of saline. After 30 minutes, animals with a load of 5% of body weight swam in a pool of water (24-26 ° C) until drowning. Recorded swimming time. The endurance of animals in relation to the control was expressed in%. The data obtained are given in table 1. The technique was used to select the optimal dose of the studied substance.

Table 1 Compound Dose mg / kg Mouse swimming time min % to control The control - 8.9 ± 2.8 one hundred Compound 10 11.3 ± 5.2 127 25 10.2 ± 5.0 115 fifty 5.9 ± 2.5 67

According to the data given in Table 1, it can be seen that the studied compound at a dose of 10 mg / kg most of all increases the endurance of mice, namely, 1.27 times with respect to the control. Next, we studied the effect of compound 1 in the optimal dose on outbred white rats males weighing 200-250 g according to the run test on a treadmill until failure.

The experiments were carried out on rats weighing 200-250 g, which ran on a treadmill to "failure". For this purpose, a four-track treadmill was used, the speed of the conveyor belt was 38-42 m / min. One rat was placed on each treadmill of the conveyor belt, in which the legs, stomach and tail were pre-wetted with water, which improved their electric shock on the trellised floor of the treadmill, through which electric current of threshold values was passed (voltage 20-30-40 V). After fatigue, the rat moves to the "electric floor", closes the chain with its paws or tail and receives a slight irritation with electric current, which forces it to leave the "electric floor" and continue to run on the treadmill. With significant fatigue, the animal does not respond to irritation of the legs with a weak electric current and remains on the "electric floor". In this case, the voltage increases to 30 V, which causes the rat to go on the treadmill and continue to run, if the stimulus is ineffective, the voltage increases to 40 V. The absence of the rat’s reaction to a shock of 40 V serves as a criterion for the complete fatigue of the animal. The rat running end time was recorded, and it was removed from the conveyor belt. This measurement served as a control. The animals rested for three days, then they were injected intraperitoneally once in the form of a thin suspension in Tween-20 at a dose of 10 mg / kg the test substance. Comparison preparations were the well-known actoprotector bemitil at a dose of 25 mg / kg and phenamine at a dose of 1.5 mg / kg (a psychomotor stimulant of a depleting type). Animals made a second run to failure 1 and 24 hours after drug administration. Endurance, expressed in%, was calculated as the ratio of the duration of the repeated run to the duration of the initial run. Each group included 8-10 animals. The data obtained are given in table.2.

table 2 Connections Dose mg / kg Rat travel time After 1 hour After 24 hours min % min % The control 16.4 ± 2.7 one hundred 16.4 ± 2.7 one hundred Bemitil 25 11.2 ± 4.7 68 19.6 ± 5.5 117 The control 22.4 ± 5.6 one hundred 22.4 ± 5.6 one hundred Phenamine 1,5 44.7 ± 6.2 * 200 * 22.4 ± 5.6 91 The control 8.1 ± 2.7 one hundred 8.1 ± 2.7 one hundred Compound 1 10 19.0 ± 3.3 ** 234 ** 14.3 ± 3.1 * 176 * Note. * - p <0.05, ** - p <0.01 in relation to the control.

Under the influence of the preparation of comparison of boehmil under the conditions of the experiment, after 1 h, the endurance was 68% of the initial level, after 24 hours this indicator increased by 17% (to 117%). Phenamine increased endurance after 1 hour significantly twice, and after 24 hours the performance indicators did not differ from the control (91% in comparison with the control). Compound 1 after 1 h increased endurance by 2.34 times, after a day - by 1.76 times, which exceeded the effect of comparison drugs.

Thus, the hydrobromide salt of ^{2-amino-4-acetyl-8-b} -gidpokci 3 ^a, 8 ^b -digidpo-thiazolo [5,4-b] indole (compound of formula 1) is superior to the known action aktoprotektornyh comparators boehmite and amphetamine, which is most pronounced 24 hours after administration, i.e. the effect of the drug should be considered as activating and long-lasting.

Claims (1)

The use of 2-amino-4-acetylthiazolo [5,4-b] indole hydrobromide of the formula

to improve performance.