UA23451C1 - - Google Patents

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DEPARTMENT AND ON THE INVENTION pon ON OO t oo tn run tn no oil (54) REMEDY FOR THE TREATMENT OF MEMORY DISORDERS 1 2 Y (21) 94063487 (57) Application of 1-adamantylatilok- (22) 16.06.94 sy-Z3-morpholino -propanol-2 hydrochloride- (24) 29.12.99 da"(adzmol) as a medicinal product ' (46) 29.12.99. Bull. Mo. 8 Means for the treatment of impaired memory. (56) Author's certificate of the USSR

Me 1829354, 1992. , (72) Zaitsev Leontiy Myronovych, Korotky

Yuriy Vasyliovych, Ivan Ivanovich Krasavtsev, Myron Onufriyovych Lozinsky, Boris Markovych Klabanov, Tetyana Voronina

Aleksandrovna (V), Khromova |rina Viktorovna (VI), Sereyedenin Sergey Borisovich (VO) (73) Institute of Organic Chemistry of the National Academy of Sciences of Ukraine

The invention relates to the field of Alzheimer's disease with a higher prevalence, 2 namely to agents that possess anti-amnestic activity and the indicated problem is solved by the use of the well-known compound 1-adamane for the treatment of impaired memory and disease Alzheimer's tylstyloxy-3-morpholino-propanol-2 c -y

Y. At the present time, there are: prepatihydrochloride (Azmol) 11), described as a drug for the treatment of memory disorders, a drug with uterostimulating activity, as well as phenibut and aminalon. 8, which is closest to the claimed Adzmol, is obtained as follows: 7 compounds by pharmacological relationship. To guests A mixture of 8.6 g (0.036 mol) of adamant

The disadvantage of these drugs is ethylethylglycidyl sulfur, 4.30 g (0.05 g high dose, in which they contain sffecmol) morpholine and 0.5 ml of heating water (2000-1000 mg/kg) and the need to wash in water bath for 10 hours, followed by a long course of treatment (1.5-6 months). excess morpholine and water are evaporated in a pyrace vacuum, and the residue is distilled. They receive there as the most frequently used 10.47 g (8996) 1-adamantyloxy-3-mor- drug for the treatment of impaired memory. folino-propanol-2, posle chego ego net-

The task is to paralyze the patient with a 1095% solution of hydrochloric acid for the treatment of impaired memory in order to obtain hydrochloride. ! t -

N

Again, 24 hours after training were spent on unrelated careers. Under the influence of sah-males weighing 180-200 g, in control animals, adzmol was administered intraperitoneally in doses of 1 and 5 mg/kg, 40 minutes before the start of the test. rement 5 dark chamber and remained there pain-

Pory mayor 1. Anti-amnestic sewing part of time. Adamol, injected into the action of Adamol was studied on the model at a dose of 1 mg/kg 40 minutes before the beginning of the training of the conditioned reaction of the passive escape. quality of amnesic factor - 10 memory from electroshock - increase in latency. period of entry into the dark compartment"

Krysam 15 minutes before the development of UR-measures and the total time of stay in

PI was injected intraperitoneally blocker M- light compartment was noted in 2.8 times on scopolamine cholinergic receptors compared to the control. in a dose of 1 mg/kg. In the future, in animals 15 In this situation, Pliracetam in a dose produced URPI in the installation of firms! 300 mg/kg, administered 40 minutes before training

And aiaisene Ipzigshitetpi (SINA). For this purpose, the Ministry of Health and the Ministry of Foreign Affairs did not show anti-amnestic effects - the animals were placed on a sanctified cloth-carrying operation in the fields. The activity of the ego form before entering the dark compartment was observed when the post-learning meter was introduced. Immediately after the first visit to the 20th canal and MZI) in approximately the same values, the animal received a measure (in the dark compartment) as in adzmol, but in a dose of 300 times the pain - an electric shock (0.6 mA), which was a seizure neck (Table 2). training The test for the preservation of the reaction of the pro-Measure 3. The effect of adzmol on the animals 24 hours after training: the animals were placed on an illuminated platform for 25 days in an orientation-research environment and their motor activity was recorded in the "open field" ". and in the dark compartment of the camera and time, pro- To study the influence of adzmol on the conducted in the lit part of the installation in the orientation-research flow of a 2-minute period. animal behavior and motor activity

When the URPI was reproduced, the control was placed in the "open field" and our animal without scopolamine was prescribed for the current 2-minute period, the registers were read to be on the lighted plate, and the number of horizontal, ver-form most of the time two-minute moved and number of the reviewed period. Under the influence of scopoladvania in the holes, the mine in the control animals was observed. in a dose of 5 mg/, with a long latent period. Adzmol at kg reduced some indicators of orien- administered 40 minutes before training had an anti-amnestic effect on training and research behavior, which is characteristic of the motor activity of rats (Table 3). terizovalos its possibility to eliminate Piracetam did not significantly change the adverse effect on the memory of the behavior of animals in the open field of scopolamine, as a result of which it is significant (Table 3). The latent period was significantly increased by Example 4. Toxicity was applied to the dark compartment of the chamber and the total 45% of my compound was determined during the acute phase of the transition in the illuminated part of the cells on unrelated muscles of both systems (by 1.7-1.8 times , table 1). la weighing 20-25 g with a single injection

Piracetam in a dose of 300 mg/kg when administered and processed according to the Litchdeny method 40 minutes before training did not eliminate Field and Wilcoxon. amnesia caused by scopolamine. BO Li of the proposed compound is 320 mg/kg. boglasno GOST 12.1.007-

Example 2. Anti-amnestic substance 76 belongs to the 2nd class (the effect of adzmol was studied on a more dangerous model) of substances. of amnesia in URPI. Thus, azmol has a pre-electroconvulsive shock (EMS) (50 Hz, 55 shocks compared to piracetam for 0.2 s) performed immediately after anti-amnestic activity and pre-training of URPI. As in the first example, the last effective dose in the test for reproducibility was carried out 60-300 times.

Table |!

Antiamnestic activity of adzmol on the scopolamine amnesia model of URPI

Latent reproduction time

Dose, time of presence

Sovdinenive deniya URPI after training and university Lu et | Calves

Control without scopolamine - " 100.5510.7 100.5310.7

Scopolamine 1 BT, 571-116

Adzmol - 5 scopolamine 1 103.5517.4 103.55:17,

Azmoly-1 scopolamine 1 98.5515.9 98.5:15.9

Piracetam. zo scopolamine 1 5BO, 8х210,8 BO, 810,8

Table 2 e Actimamnestic activity of zdzmol on the model of shock amnesia URPI

Latentnov vremya vosproizve- . Dose, Time of presence with - Summing up mg/kg day of URPI after training and in the bright compartment of vamnesia

Control without poka - 120.0514.8 120.0::14.8

Control with shock 25,528.52 25,548.59

Adzmol 708315, 70.6x152

Piracetam (before her training and shock) z00 24,559.8 24.5:29.8

Piracetam (after 7 training m of shock) from 60.7 to 17.5 60.7 to 17.3

Table 3

Influenced by adamol on orientation and research hunting and motor activity in the open field

Dose, 1 horizontal - Total

The combination of "mg/kg of visible and vertical |" Lukaszately oh to! in the holes of the racks

Control - 19.3523.7 7514 9.530.7 36.3-4.0

Adamol 1 15,153.6 471.4 6,050, 25,854.7

Piracetam B 14.6-1.87 Abzh1, 66.5 25.81, 00 18.723.2 812321 LEZY 35.923.5 o r « 0.05, Reliability of differences between control with amnesia and without amnesia, 7 Rie 0, 05. The reliability of the differences between the total and control (with amnesia) groups according to Student.

AND

! . and 1 '

Compiler Tehred M. Kelemesh Proofreader M. Samborska

Order 535 Circulation Signature

State Patent Office of Ukraine, 254655, GOSP, Kyiv-53, Lvivska Square, 8

Open joint-stock company "Patent", Uzhgorod, st. Gagarina, 101