title: ÐÐµÑ Ð°Ð½Ð¸Ð·Ð¼Ñ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ñ NMDA ÑÐµÑÐµÐ¿ÑÐ¾ÑÐ¾Ð² Ð¿ÐµÐ½ÑÐ°Ð¼Ð¸Ð´Ð¸Ð½Ð¾Ð¼ Ð¸ Ð´Ð¸Ð¼Ð¸Ð½Ð°Ð·Ð¸Ð½Ð¾Ð¼
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð±Ð°ÐºÐ°Ð»Ð°Ð²ÑÐ°
titleType: Subtitle
title: Mechanisms of NMDA receptor inhibition by pentamidine and diminazene
Creators: name: ÐÐ¸Ð³ÑÐ»Ð¸Ð½, ÐÑÑÐµÐ½Ð¸Ð¹
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: 2019
Subjects: Ð¿ÐµÐ½ÑÐ°Ð¼Ð¸Ð´Ð¸Ð½
Ð´Ð¸Ð¼Ð¸Ð½Ð°Ð·Ð¸Ð½
NMDA ÑÐµÑÐµÐ¿ÑÐ¾ÑÑ
Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ
Ð¿Ð°ÑÑ-ÐºÐ»Ð°Ð¼Ð¿
Ð¼ÐµÑ Ð°Ð½Ð¸Ð·Ð¼Ñ
pentamidine
diminazene
NMDA receptors
inhibition
patch-clamp
mechanisms

description: ÐÐµÐ½ÑÐ°Ð¼Ð¸Ð´Ð¸Ð½ Ð¸ Ð´Ð¸Ð¼Ð¸Ð½Ð°Ð·Ð¸Ð½ â ÑÑÐ¾ Ð´Ð²Ð° Ð´Ð¸Ð°Ð¼Ð¸Ð´Ð¸Ð½Ð¾Ð²ÑÑ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ñ, Ð¸ÑÐ¿Ð¾Ð»ÑÐ·ÑÐµÐ¼ÑÑ Ð² ÐºÐ°ÑÐµÑÑÐ²Ðµ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾Ð¼Ð¸ÐºÑÐ¾Ð±Ð½ÑÑ Ð¿ÑÐµÐ¿Ð°ÑÐ°ÑÐ¾Ð². Ð Ð´Ð°Ð½Ð½Ð¾Ð¹ ÑÐ°Ð±Ð¾ÑÐµ Ð¿Ð¾ÐºÐ°Ð·ÑÐ²Ð°ÐµÑÑÑ, ÑÑÐ¾ Ð´Ð°Ð½Ð½ÑÐµ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ñ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÑÑÑ NMDA ÑÐµÑÐµÐ¿ÑÐ¾ÑÑ ÐºÐ¾Ð½ÑÐµÐ½ÑÑÐ°ÑÐ¸Ð¾Ð½Ð½Ð¾-Ð·Ð°Ð²Ð¸ÑÐ¸Ð¼ÑÐ¼ Ð¾Ð±ÑÐ°Ð·Ð¾Ð¼. ÐÐ½Ð³Ð¸Ð±Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ Ð¿ÐµÐ½ÑÐ°Ð¼Ð¸Ð´Ð¸Ð½Ð¾Ð¼ ÑÐ²Ð»ÑÐµÑÑÑ Ð¾Ð¿ÑÐµÐ´ÐµÐ»ÑÐ½Ð½Ð¾ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»-Ð·Ð°Ð²Ð¸ÑÐ¸Ð¼ÑÐ¼, Ñ Ð´Ð¸Ð¼Ð¸Ð½Ð°Ð·Ð¸Ð½Ð° Ð½Ð°Ð±Ð»ÑÐ´Ð°ÑÑÑÑ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»-Ð·Ð°Ð²Ð¸ÑÐ¸Ð¼Ð°Ñ Ð¸ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»-Ð½ÐµÐ·Ð°Ð²Ð¸ÑÐ¸Ð¼Ð°Ñ ÐºÐ¾Ð¼Ð¿Ð¾Ð½ÐµÐ½ÑÑ. ÐÐ¸Ð¼Ð¸Ð½Ð°Ð·Ð¸Ð½ Ð´ÐµÐ¼Ð¾Ð½ÑÑÑÐ¸ÑÑÐµÑ ÑÐ²Ð¾ÑÑÐ¾Ð²ÑÐµ ÑÐ¾ÐºÐ¸ Ð¸ Ð¾Ð²ÐµÑÑÑÑÑ, ÑÑÐ¾ Ð³Ð¾Ð²Ð¾ÑÐ¸Ñ Ð¾ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ð¸ Ð¿Ð¾ Ð¼ÐµÑÐ°Ð½Ð¸Ð·Ð¼Ñ Â«foot-in-the-doorÂ». ÐÐµÐ½ÑÐ°Ð¼Ð¸Ð´Ð¸Ð½ Ð¶Ðµ Ð¿ÑÐ¾ÑÐ²Ð»ÑÐµÑ ÑÐ°ÑÑÐ¸ÑÐ½ÑÑ Ð»Ð¾Ð²ÑÑÐºÑ Ð² Ð·Ð°ÐºÑÑÑÐ¾Ð¼ ÐºÐ°Ð½Ð°Ð»Ðµ NMDA ÑÐµÑÐµÐ¿ÑÐ¾ÑÐ°. Ð¢Ð°ÐºÐ¾Ðµ ÑÐ°Ð·Ð»Ð¸ÑÐ¸Ðµ Ð² Ð¼ÐµÑÐ°Ð½Ð¸Ð·Ð¼Ðµ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ñ Ð¼Ð¾Ð¶ÐµÑ Ð±ÑÑÑ Ð¾Ð±ÑÑÑÐ½ÐµÐ½Ð¾ Ð¾ÑÐ»Ð¸ÑÐ¸ÑÐ¼Ð¸ 3D ÑÑÑÑÐºÑÑÑÑ Ð´Ð°Ð½Ð½ÑÑ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ð¹. Ð Ð¼Ð¾Ð»ÐµÐºÑÐ»Ðµ Ð¿ÐµÐ½ÑÐ°Ð¼Ð¸Ð´Ð¸Ð½Ð° Ð´Ð²Ðµ Ð±ÐµÐ½Ð·Ð°Ð¼Ð¸Ð´Ð¸Ð½Ð¾Ð²ÑÐµ Ð³ÑÑÐ¿Ð¿Ñ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ñ Ð³Ð¸Ð±ÐºÐ¸Ð¼ Ð»Ð¸Ð½ÐºÐµÑÐ¾Ð¼, ÑÑÐ¾ Ð¿Ð¾Ð·Ð²Ð¾Ð»ÑÐµÑ Ð¼Ð¾Ð»ÐµÐºÑÐ»Ðµ ÑÐºÐ»Ð°Ð´ÑÐ²Ð°ÑÑÑÑ Ð¸ Ð¿Ð¾Ð¼ÐµÑÐ°ÑÑÑÑ Ð²Ð½ÑÑÑÐ¸ Ð·Ð°ÐºÑÑÑÐ¾Ð³Ð¾ NMDA ÐºÐ°Ð½Ð°Ð»Ð°. ÐÐ¸Ð¼Ð¸Ð½Ð°Ð·Ð¸Ð½ Ð¶Ðµ Ð¸Ð¼ÐµÐµÑ Ð¶ÑÑÑÐºÑÑ ÑÑÑÑÐºÑÑÑÑ Ð¸ Ð½Ðµ Ð¼Ð¾Ð¶ÐµÑ Ð¾ÐºÐ°Ð·Ð°ÑÑÑÑ Ð² Ð»Ð¾Ð²ÑÑÐºÐµ.
description: Pentamidine and diminazene are anti-protozoal diarylamidine compounds. In this study we show that they inhibit NâmethylâDâaspartate (NMDA) receptors in a concentration-dependent manner. The inhibition by pentamidine was strongly voltage-dependent, while that of diminazene had voltage-independent components. Diminazene demonstrated tail currents and overshoots suggesting âfoot-in-the-doorâ mechanism of action. In contrast, pentamidine was partially trapped in the closed NMDA receptor channels. Such difference in the mechanism of action can be explained by the difference in the 3D structure of compounds. In the pentamidine molecule two benzamidine groups are connected with a flexible linker, which allows the molecule to fold up and fit in the cavity of a closed NMDA receptor channel. Diminazene, in contrast, has an extended form and could not be trapped.