title: ÐÐ½ÑÐ¸Ð¿Ð°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð¸ÑÐµÑÐºÐ¾Ðµ Ð¸ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾ÑÑÐ´Ð¾ÑÐ¾Ð¶Ð½Ð¾Ðµ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ðµ Ð½Ð¾Ð²ÑÑ Ð»Ð¸Ð³Ð°Ð½Ð´Ð¾Ð² NMDA-ÑÐµÑÐµÐ¿ÑÐ¾ÑÐ¾Ð²
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: Anti-Parkinsonian and anticonvulsant effects of the new ligands of NMDA-receptors
Creators: name: Ð¡Ð¸ÑÐ´Ð¸ÐºÐ¾Ð²Ð°, ÐÑÐµÐ½Ð¸Ñ
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2022
Subjects: ÐÐ¸Ð¾ÑÐ¸Ð·Ð¸ÐºÐ°
Ð°Ð½ÑÐ°Ð³Ð¾Ð½Ð¸ÑÑÑ NMDA-ÑÐµÑÐµÐ¿ÑÐ¾ÑÐ¾Ð²
Ð±Ð¾Ð»ÐµÐ·Ð½Ñ ÐÐ°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð°
ÑÑÐ´Ð¾ÑÐ¾Ð³Ð¸
Ð¿ÑÐ¾Ð¸Ð·Ð²Ð¾Ð´Ð½ÑÐµ Ð¸Ð¼Ð¸Ð´Ð°Ð·Ð¾Ð»-4
5-Ð´Ð¸ÐºÐ°ÑÐ±Ð¾Ð½Ð¾Ð²Ð¾Ð¹ ÐºÐ¸ÑÐ»Ð¾ÑÑ
Ð¿ÑÐ¾Ð¸Ð·Ð²Ð¾Ð´Ð½ÑÐµ ÑÐµÐ½Ð¸Ð»ÑÐ¸ÐºÐ»Ð¾Ð³ÐµÐºÑÐ¸Ð»Ð°
NMDA receptor ligands
Parkinson's disease
seizures
imidazole-4
5-dicarboxylic acid derivatives
phenylcyclohexyl derivatives

description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸Ð·ÑÑÐµÐ½Ð¸Ñ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾Ð¿Ð°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð¸ÑÐµÑÐºÐ¾Ð³Ð¾ Ð¸ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾ÑÑÐ´Ð¾ÑÐ¾Ð¶Ð½Ð¾Ð³Ð¾ ÑÑÑÐµÐºÑÐ° Ð½Ð¾Ð²ÑÑ Ð»Ð¸Ð³Ð°Ð½Ð´Ð¾Ð² NMDA-ÑÐµÑÐµÐ¿ÑÐ¾ÑÐ¾Ð² Ð² ÑÐºÑÐ¿ÐµÑÐ¸Ð¼ÐµÐ½ÑÐ°Ð»ÑÐ½ÑÑ Ð¼Ð¾Ð´ÐµÐ»ÑÑ ÑÑÐ´Ð¾ÑÐ¾Ð³ Ð¸ Ð¿Ð°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð¸Ð·Ð¼Ð° Ñ Ð¼ÑÑÐµÐ¹. Ð Ð´Ð°Ð½Ð½Ð¾Ð¹ ÑÐ°Ð±Ð¾ÑÐµ Ð½Ð° Ð¼Ð¾Ð´ÐµÐ»ÑÑ Ð½Ð¸ÐºÐ¾ÑÐ¸Ð½-Ð¸Ð½Ð´ÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÑ Ð¸ ÐºÐ¾ÑÐ°Ð·Ð¾Ð»-Ð¸Ð½Ð´ÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÑ ÑÑÐ´Ð¾ÑÐ¾Ð³ Ñ Ð¼ÑÑÐµÐ¹ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð»Ð¸ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾ÑÑÐ´Ð¾ÑÐ¾Ð¶Ð½ÑÑ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ ÑÑÐµÑ Ð»Ð¸Ð³Ð°Ð½Ð´Ð¾Ð² NMDA-ÑÐµÑÐµÐ¿ÑÐ¾ÑÐ¾Ð²: Ð¿ÑÐ¾Ð¸Ð·Ð²Ð¾Ð´Ð½Ð¾Ð³Ð¾ ÑÐµÐ½Ð¸Ð»ÑÐ¸ÐºÐ»Ð¾Ð³ÐµÐºÑÐ¸Ð»Ð° (ÐÐ­Ð-2044) Ð¸ Ð¿ÑÐ¾Ð¸Ð·Ð²Ð¾Ð´Ð½ÑÑ Ð¸Ð¼Ð¸Ð´Ð°Ð·Ð¾Ð»-4,5-Ð´Ð¸ÐºÐ°ÑÐ±Ð¾Ð½Ð¾Ð²ÑÑ ÐºÐ¸ÑÐ»Ð¾Ñ (ÐÐ­Ð-2295, ÐÐ­Ð-2296). ÐÐ½Ð°Ð»Ð¸Ð· Ð¿ÑÐ¾Ð²Ð¾Ð´Ð¸Ð»ÑÑ Ð¿ÑÐ¸ ÑÑÐ°Ð²Ð½ÐµÐ½Ð¸Ð¸ Ð² ÑÐµÑÑÐ¸ÑÑÐµÐ¼Ð¾Ð¹ Ð¸ ÐºÐ¾Ð½ÑÑÐ¾Ð»ÑÐ½Ð¾Ð¹ Ð³ÑÑÐ¿Ð¿ ÑÐ»ÐµÐ´ÑÑÑÐ¸Ñ Ð¿Ð°ÑÐ°Ð¼ÐµÑÑÐ¾Ð²: Ð´Ð»Ð¸ÑÐµÐ»ÑÐ½Ð¾ÑÑÑ Ð¸ Ð¸Ð½ÑÐµÐ½ÑÐ¸Ð²Ð½Ð¾ÑÑÑ ÑÑÐ´Ð¾ÑÐ¾Ð³, Ð¿ÑÐ¾Ð´Ð¾Ð»Ð¶Ð¸ÑÐµÐ»ÑÐ½Ð¾ÑÑÑ Ð»Ð°ÑÐµÐ½ÑÐ½Ð¾Ð³Ð¾ Ð¿ÐµÑÐ¸Ð¾Ð´Ð°, ÑÐ°ÑÑÐ¾ÑÐ° Ð»ÐµÑÐ°Ð»ÑÐ½ÑÑ Ð¸ÑÑÐ¾Ð´Ð¾Ð² Ð¸ Ð¸Ð½ÑÐµ ÑÐµÐ°ÐºÑÐ¸Ð¸. ÐÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¾ Ð²Ð»Ð¸ÑÐ½Ð¸Ðµ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ñ ÐÐ­Ðâ2295 Ð½Ð° Ð¿Ð¾Ð²ÐµÐ´ÐµÐ½Ð¸Ðµ Ð¼ÑÑÐµÐ¹ Ñ 6-OHDA-Ð¸Ð½Ð´ÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÐ¼ Ð¿Ð°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð¸Ð·Ð¼Ð¾Ð¼ (Ð² ÑÐµÑÑÐ°Ñ Â«ÐÑÐºÑÑÑÐ¾Ðµ Ð¿Ð¾Ð»ÐµÂ», Pole-ÑÐµÑÑ, ÑÐ¾ÑÐ°ÑÐ¾Ð´), Ð° ÑÐ°ÐºÐ¶Ðµ ÐµÐ³Ð¾ Ð²Ð»Ð¸ÑÐ½Ð¸Ðµ Ð½Ð° ÑÐºÑÐ¿ÑÐµÑÑÐ¸Ñ ÑÑÐ±ÑÐµÐ´Ð¸Ð½Ð¸Ñ GluN2A-GluN2D Ð² Ð¿Ð¾Ð»Ð¾ÑÐ°ÑÐ¾Ð¼ ÑÐµÐ»Ðµ Ð² Ð´Ð°Ð½Ð½Ð¾Ð¹ ÑÐºÑÐ¿ÐµÑÐ¸Ð¼ÐµÐ½ÑÐ°Ð»ÑÐ½Ð¾Ð¹ Ð¼Ð¾Ð´ÐµÐ»Ð¸ Ð¼ÐµÑÐ¾Ð´Ð¾Ð¼ ÐÐ¢-ÐÐ¦Ð  Ð² ÑÐµÐ°Ð»ÑÐ½Ð¾Ð¼ Ð²ÑÐµÐ¼ÐµÐ½Ð¸. Ð£ÑÑÐ°Ð½Ð¾Ð²Ð»ÐµÐ½Ð¾, ÑÑÐ¾ Ð²ÐµÑÐµÑÑÐ²Ð¾ ÐÐ­Ð-2044 Ð¿ÑÐ¾ÑÐ²Ð»ÑÐµÑ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾ÑÑÐ´Ð¾ÑÐ¾Ð¶Ð½ÑÑ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ, ÑÐ½Ð¸Ð¶Ð°ÐµÑ Ð²ÐµÑÐ¾ÑÑÐ½Ð¾ÑÑÑ Ð»ÐµÑÐ°Ð»ÑÐ½Ð¾Ð³Ð¾ Ð¸ÑÑÐ¾Ð´Ð° Ð¸ Ð²ÐµÑÐ¾ÑÑÐ½Ð¾ÑÑÑ ÑÐ°Ð·Ð²Ð¸ÑÐ¸Ñ ÑÑÐ´Ð¾ÑÐ¾Ð¶Ð½Ð¾Ð³Ð¾ Ð¿ÑÐ¸ÑÑÑÐ¿Ð°. Ð¡Ð¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ðµ ÐÐ­Ð-2295 Ð¿ÑÐ¾ÑÐ²Ð»ÑÐµÑ Ð°Ð½ÑÐ¸Ð¿Ð°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÑÑÐµÐºÑ, Ð¿ÑÐµÐ´Ð¾ÑÐ²ÑÐ°ÑÐ°Ñ ÑÐ½Ð¸Ð¶ÐµÐ½Ð¸Ðµ Ð»Ð¾ÐºÐ¾Ð¼Ð¾ÑÐ¾ÑÐ½Ð¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ñ Ð¼ÑÑÐµÐ¹ Ð² Ð¼Ð¾Ð´ÐµÐ»Ð¸ Ð¿Ð°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð¸Ð·Ð¼Ð°. Ð¢Ð°ÐºÐ¸Ð¼ Ð¾Ð±ÑÐ°Ð·Ð¾Ð¼, Ð²ÐµÑÐµÑÑÐ²Ð¾ ÐÐ­Ð-2295 Ð¿ÐµÑÑÐ¿ÐµÐºÑÐ¸Ð²Ð½Ð¾ Ð´Ð»Ñ Ð²Ð¾Ð·Ð¼Ð¾Ð¶Ð½Ð¾Ð³Ð¾ Ð¿ÑÐ¸Ð¼ÐµÐ½ÐµÐ½Ð¸Ñ Ð² ÐºÐ¾Ð¼Ð±Ð¸Ð½Ð¸ÑÐ¾Ð²Ð°Ð½Ð½Ð¾Ð¹ ÑÐµÑÐ°Ð¿Ð¸Ð¸ Ð±Ð¾Ð»ÐµÐ·Ð½Ð¸ ÐÐ°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð°. ÐÑÐ¸ ÑÑÐ¾Ð¼, Ð´Ð°Ð½Ð½Ð¾Ðµ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ðµ Ð½Ðµ Ð¿Ð¾ÐºÐ°Ð·Ð°Ð»Ð¾ Ð²ÑÑÐ°Ð¶ÐµÐ½Ð½Ð¾Ð¹ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾ÑÑÐ´Ð¾ÑÐ¾Ð¶Ð½Ð¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸. ÐÑÐ¾ÑÐ¸Ð²Ð¾Ð¿Ð¾Ð»Ð¾Ð¶Ð½ÑÐµ Ð´Ð°Ð½Ð½ÑÐµ Ð±ÑÐ»Ð¸ Ð¿Ð¾Ð»ÑÑÐµÐ½Ñ Ð´Ð»Ñ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ñ ÐÐ­Ð-2296, ÐºÐ¾ÑÐ¾ÑÐ¾Ðµ ÑÑÐ¸Ð»Ð¸Ð²Ð°Ð»Ð¾ Ð¸Ð½ÑÐµÐ½ÑÐ¸Ð²Ð½Ð¾ÑÑÑ ÑÑÐ´Ð¾ÑÐ¾Ð³ Ð¸ ÑÐ²ÐµÐ»Ð¸ÑÐ¸Ð²Ð°Ð»Ð¾ Ð²ÐµÑÐ¾ÑÑÐ½Ð¾ÑÑÑ Ð»ÐµÑÐ°Ð»ÑÐ½ÑÑ Ð¸ÑÑÐ¾Ð´Ð¾Ð² Ð² Ð¿ÑÐ¸ÑÑÑÑÑÐ²Ð¸Ð¸ ÐºÐ¾Ð½Ð²ÑÐ»ÑÑÐ°Ð½ÑÐ°. Ð¡ ÑÑÐµÑÐ¾Ð¼ Ð¿Ð¾Ð»ÑÑÐµÐ½Ð½ÑÑ Ð´Ð°Ð½Ð½ÑÑ Ð¼Ð¾Ð¶Ð½Ð¾ Ð³Ð¾Ð²Ð¾ÑÐ¸ÑÑ Ð¾Ð± ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾Ð¼ Â Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾ÑÑÐ´Ð¾ÑÐ¾Ð¶Ð½Ð¾Ð¼ Ð¸ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾Ð¿Ð°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð¸ÑÐµÑÐºÐ¾Ð¼ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ð¸ Ð½ÐµÐºÐ¾ÑÐ¾ÑÑÑ Ð»Ð¸Ð³Ð°Ð½Ð´Ð¾Ð² NMDA-ÑÐµÑÐµÐ¿ÑÐ¾ÑÐ¾Ð², Ð° ÑÐ»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»ÑÐ½Ð¾ Ð¸ Ð¾ Ð¿ÐµÑÑÐ¿ÐµÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð¸Ñ ÑÐ°Ð·ÑÐ°Ð±Ð¾ÑÐºÐ¸ Ñ ÑÐµÐ»ÑÑ Ð´Ð°Ð»ÑÐ½ÐµÐ¹ÑÐµÐ³Ð¾ Ð²Ð¾Ð·Ð¼Ð¾Ð¶Ð½Ð¾Ð³Ð¾ Ð¿ÑÐ¸Ð¼ÐµÐ½ÐµÐ½Ð¸Ð¸ Ð² ÑÐµÑÐ°Ð¿Ð¸Ð¸ ÑÑÐ´Ð¾ÑÐ¾Ð¶Ð½ÑÑ ÑÐ°ÑÑÑÑÐ¾Ð¹ÑÑÐ² Ð¸ Ð±Ð¾Ð»ÐµÐ·Ð½Ð¸ ÐÐ°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð°.
description: The given work is devoted to the study of the anti-Parkinsonian and anticonvulsant effects of the new NMDA receptor antagonists in experimental models of seizures and Parkinson's disease. In this work was studied the anticonvulsant activity of three NMDA receptor ligands on models of nicotine-induced and PTZ-induced seizures in mice: a phenylcyclohexyl derivative (IEM-2044) and imidazole-4,5-dicarboxylic acid derivatives (IEM-2295, IEM-2296). The analysis was carried out by comparing the following parameters in the test and control groups: the duration and intensity of seizures, the duration of the latent period, the frequency of deaths and other reactions. The effect of the Â compound IEM-2295 on the behavior of mice with 6âOHDA-induced parkinsonism (in the Â«Open FieldÂ», Pole-test, rotarod tests), as well as its effect on the expression of GluN2A-GluN2D subunits in the striatum in this animal model, was studied using the RT-PCR in real time. It has been established that the substance IEM-2044 exhibits anticonvulsant activity, reduces the likelihood of death and the likelihood of developing a seizure. The compound IEM-2295 exhibits an antiparkinsonian effect, preventing a decrease in locomotor activity in mice in a model of parkinsonism. Thus, the substance IEMâ2295 is promising for possible use in the combination therapy of Parkinson's disease. At the same time, this compound did not show a pronounced anticonvulsant activity. Opposite data were obtained for the compound IEM-2296, which increased the intensity of convulsions and increased the likelihood of death in the presence of a convulsant. Considering the data obtained, we can speak about the effective anticonvulsant and antiparkinsonian effect of some NMDA receptor ligands, and therefore about the prospects for their development with a view to further possible use in the treatment of convulsive disorders and Parkinson's disease.