title: ÐÐµÑ Ð°Ð½Ð¸Ð·Ð¼Ñ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ñ ÑÑÐ¸ÑÐ¸ÐºÐ»Ð¸ÑÐµÑÐºÐ¾Ð³Ð¾ Ð°Ð½ÑÐ¸Ð´ÐµÐ¿ÑÐµÑÑÐ°Ð½ÑÐ° Ð°Ð¼Ð¸ÑÑÐ¸Ð¿ÑÐ¸Ð»Ð¸Ð½Ð° Ð½Ð° Ð³Ð»ÑÑÐ°Ð¼Ð°ÑÐµÑÐ³Ð¸ÑÐµÑÐºÑÑ ÑÐ¸ÑÑÐµÐ¼Ñ
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: The mechanisms of action of the tricyclic antidepressant amitriptyline on the glutamatergic system
Creators: name: ÐÐ¾Ð¹ÐºÐ¾Ð², Ð¡ÐµÑÐ³ÐµÐ¹
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: 2020
Subjects: Ð°Ð¼Ð¸ÑÑÐ¸Ð¿ÑÐ¸Ð»Ð¸Ð½
NMDA-ÑÐµÑÐµÐ¿ÑÐ¾Ñ
Ð½ÐµÐ¹ÑÐ¾Ð½
Ð¿ÑÑÑ-ÐºÐ»Ð°Ð¼Ð¿
Ð¿ÐµÑÐ²Ð¸ÑÐ½Ð°Ñ ÐºÑÐ»ÑÑÑÑÐ°
Ð¾ÑÐºÑÑÑÑÐ¹ ÐºÐ°Ð½Ð°Ð»ÑÐ½ÑÐ¹ Ð±Ð»Ð¾Ðº
amitriptyline
NMDA-receptor
neuron
patch-clamp
primary culture
open-channel block

description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸Ð·ÑÑÐµÐ½Ð¸Ñ Ð¼ÐµÑÐ°Ð½Ð¸Ð·Ð¼Ð¾Ð² Ð´ÐµÐ¹ÑÑÐ²Ð¸Ñ Ð°Ð¼Ð¸ÑÑÐ¸Ð¿ÑÐ¸Ð»Ð¸Ð½Ð° (ATL) Ð½Ð° NMDA-ÑÐµÑÐµÐ¿ÑÐ¾ÑÑ (NMDAR). Ð¦ÐµÐ»ÑÑ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð¾ Ð¸Ð·ÑÑÐµÐ½Ð¸Ðµ Ð¼ÐµÑÐ°Ð½Ð¸Ð·Ð¼Ð¾Ð² Ð²Ð»Ð¸ÑÐ½Ð¸Ñ ATL Ð½Ð° NMDAR Ð³Ð»ÑÑÐ°Ð¼Ð°ÑÐµÑÐ³Ð¸ÑÐµÑÐºÐ¾Ð¹ ÑÐ¸ÑÑÐµÐ¼Ñ Ð½ÐµÐ¹ÑÐ¾Ð½Ð¾Ð² ÐºÐ¾ÑÑ. ÐÐ°Ð´Ð°ÑÐ¸, ÐºÐ¾ÑÐ¾ÑÑÐµ ÑÐµÑÐ°Ð»Ð¸ÑÑ Ð² ÑÐ¾Ð´Ðµ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ: 1. Ð¡ÑÐ°Ð²Ð½Ð¸ÑÑ ÑÑÑÐµÐºÑÑ ÐºÐ¾Ð½ÑÐµÐ½ÑÑÐ°ÑÐ¸Ð¹ ATL Ð½Ð° ÑÐ¾ÐºÐ¸ NMDAR Ð² Ð·Ð°Ð²Ð¸ÑÐ¸Ð¼Ð¾ÑÑÐ¸ Ð¾Ñ Ð¼ÐµÐ¼Ð±ÑÐ°Ð½Ð½Ð¾Ð³Ð¾ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»Ð°; 2. ÐÑÐ¾Ð²ÐµÑÐ¸ÑÑ Ð²Ð»Ð¸ÑÐ½Ð¸Ðµ Ð²Ð½ÐµÐºÐ»ÐµÑÐ¾ÑÐ½Ð¾Ð³Ð¾ ÐºÐ°Ð»ÑÑÐ¸Ñ Ð½Ð° Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ ATL NMDA-Ð¾Ð¿Ð¾ÑÑÐµÐ´Ð¾Ð²Ð°Ð½Ð½ÑÑ ÑÐ¾ÐºÐ¾Ð²; 3. ÐÐ¿ÑÐµÐ´ÐµÐ»Ð¸ÑÑ Ð¿Ð°ÑÐ°Ð¼ÐµÑÑÑ Ð±Ð»Ð¾ÐºÐ° Ð¾ÑÐºÑÑÑÑÑ ÐºÐ°Ð½Ð°Ð»Ð¾Ð² NMDAR; 4. ÐÐ¾Ð»ÑÑÐ¸ÑÑ Ð·Ð½Ð°ÑÐµÐ½Ð¸Ñ IC50 ÑÐ¾ÐºÐ¾Ð² NMDAR Ð´Ð»Ñ ATL Ð² Ð·Ð°Ð²Ð¸ÑÐ¸Ð¼Ð¾ÑÑÐ¸ Ð¾Ñ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»Ð°; 5. ÐÑÐ¾Ð²ÐµÑÐ¸ÑÑ Ð²Ð¾Ð·Ð¼Ð¾Ð¶Ð½Ð¾Ðµ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ðµ ATL Ð½Ð° Ð·Ð°ÐºÑÑÑÑÐ¹ ÐºÐ°Ð½Ð°Ð» NMDAR; 6. ÐÑÐ¾Ð°Ð½Ð°Ð»Ð¸Ð·Ð¸ÑÐ¾Ð²Ð°ÑÑ Â«ÑÑÑÐµÐºÑ Ð»Ð¾Ð²ÑÑÐºÐ¸Â» Ð¿ÑÐ¸ Ð±Ð»Ð¾ÐºÐ¸ÑÐ¾Ð²Ð°Ð½Ð¸Ð¸ Ð¾ÑÐºÑÑÑÑÑ ÐºÐ°Ð½Ð°Ð»Ð¾Ð² NMDAR ATL. ÐÑÐ» Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°Ð½ ÑÐ»ÐµÐºÑÑÐ¾ÑÐ¸Ð·Ð¸Ð¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ð¹ Ð¼ÐµÑÐ¾Ð´ Ð¿ÑÑÑ-ÐºÐ»Ð°Ð¼Ð¿ Ð´Ð»Ñ Ð¸Ð·ÑÑÐµÐ½Ð¸Ñ ÑÑÑÐµÐºÑÐ¾Ð² ATL Ð½Ð° ÑÐ¾ÐºÐ¸ NMDAR Ð¸ ÐºÐ°Ð»ÑÑÐ¸ÐµÐ²Ð¾Ð³Ð¾ Ð¸Ð¼Ð¸Ð´Ð¶Ð¸Ð½Ð³Ð° Ð´Ð»Ñ ÑÐµÐ³Ð¸ÑÑÑÐ°ÑÐ¸Ð¸ ÐºÐ°Ð»ÑÑÐ¸ÐµÐ²ÑÑ Ð¾ÑÐ²ÐµÑÐ¾Ð² Ð²Ð½ÑÑÑÐ¸ Ð½ÐµÐ¹ÑÐ¾Ð½Ð¾Ð² Ð¿ÐµÑÐ²Ð¸ÑÐ½Ð¾Ð¹ ÐºÑÐ»ÑÑÑÑÑ ÐºÐ¾ÑÑ in vitro. Ð ÑÐµÐ·ÑÐ»ÑÑÐ°ÑÐµ Ð±ÑÐ»Ð¸ ÑÑÐ°Ð²Ð½ÐµÐ½Ñ ÑÑÑÐµÐºÑÑ ÐºÐ¾Ð½ÑÐµÐ½ÑÑÐ°ÑÐ¸Ð¹ ATL Ð½Ð° ÑÐ¾ÐºÐ¸ NMDAR Ð² Ð·Ð°Ð²Ð¸ÑÐ¸Ð¼Ð¾ÑÑÐ¸ Ð¾Ñ Ð¼ÐµÐ¼Ð±ÑÐ°Ð½Ð½Ð¾Ð³Ð¾ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»Ð°, Ð²ÑÑÐ²Ð»ÐµÐ½Ð¾ Ð·Ð½Ð°ÑÐ¸ÑÐµÐ»ÑÐ½Ð¾Ðµ Ð²Ð»Ð¸ÑÐ½Ð¸Ðµ Ð²Ð½ÐµÐºÐ»ÐµÑÐ¾ÑÐ½Ð¾Ð³Ð¾ ÐºÐ°Ð»ÑÑÐ¸Ñ Ð½Ð° Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ ATL ÑÐ¾ÐºÐ¾Ð² NMDAR, Ð¾Ð¿ÑÐµÐ´ÐµÐ»ÐµÐ½Ñ Ð¿Ð°ÑÐ°Ð¼ÐµÑÑÑ Ð±Ð»Ð¾ÐºÐ° Ð¾ÑÐºÑÑÑÑÑ ÐºÐ°Ð½Ð°Ð»Ð¾Ð². ÐÑÑÐ²Ð»ÐµÐ½Ð¾, ÑÑÐ¾ ATL Ð½Ðµ Ð´ÐµÐ¹ÑÑÐ²ÑÐµÑ Ð½Ð° Ð·Ð°ÐºÑÑÑÑÐ¹ ÐºÐ°Ð½Ð°Ð» Ð¸ ÑÐ²Ð»ÑÐµÑÑÑ Ð±Ð»Ð¾ÐºÐ°ÑÐ¾ÑÐ¾Ð¼ Ð¾ÑÐºÑÑÑÐ¾Ð³Ð¾ ÐºÐ°Ð½Ð°Ð»Ð° NMDAR (Ð¿Ð¾ÐºÐ°Ð·ÑÐ²Ð°ÐµÑ "ÑÐ°ÑÑÐ¸ÑÐ½ÑÑ Ð»Ð¾Ð²ÑÑÐºÑ"), Ð¿Ð°ÑÐ°Ð¼ÐµÑÑÑ Ð±Ð»Ð¾ÐºÐ° ÑÑÐ¾Ð¶Ð¸ Ñ ÐºÐ»Ð¸Ð½Ð¸ÑÐµÑÐºÐ¸ Ð·Ð½Ð°ÑÐ¸Ð¼ÑÐ¼Ð¸ Ð±Ð»Ð¾ÐºÐ°ÑÐ¾ÑÐ°Ð¼Ð¸. ÐÐ¾Ð»ÑÑÐµÐ½Ð½ÑÐµ Ð´Ð°Ð½Ð½ÑÐµ ÑÐ²Ð»ÑÑÑÑÑ Ð²Ð°Ð¶Ð½ÑÐ¼Ð¸ Ð´Ð»Ñ Ð¿Ð¾Ð½Ð¸Ð¼Ð°Ð½Ð¸Ñ Ð±Ð¸Ð¾ÑÐ¸Ð·Ð¸ÑÐµÑÐºÐ¸Ñ ÑÐ²Ð¾Ð¹ÑÑÐ² NMDAR, Ð° ÑÐ°ÐºÐ¶Ðµ ÐºÐ»Ð¸Ð½Ð¸ÑÐµÑÐºÐ¸Ð¼Ð¸ Ð·Ð½Ð°ÑÐ¸Ð¼ÑÐ¼Ð¸ Ð´Ð»Ñ ÑÐ°ÑÑÐ¸ÑÐµÐ½Ð¸Ñ Ð¿ÑÐµÐ´ÑÑÐ°Ð²Ð»ÐµÐ½Ð¸Ð¹ Ð¾ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ð¸ Ð°Ð½ÑÐ¸Ð´ÐµÐ¿ÑÐµÑÑÐ°Ð½ÑÐ¾Ð² Ð½Ð° Ð¦ÐÐ¡ ÑÐµÐ»Ð¾Ð²ÐµÐºÐ°.
description: The work is devoted to studying the mechanisms of action of amitriptyline (ATL) on NMDA-receptors (NMDAR). The aim was the study the mechanisms of ATL influence on NMDAR of the glutamatergic system. The research set the following goals: 1. Compare the effects of ATL concentrations on NMDAR currents depending on membrane potential; 2. Check the effect of extracellular calcium on the inhibition by ATL NMDA mediated currents; 3. Determine open-channel block parameters of NMDAR; 4. Obtain IC50 values of NMDAR currents for ATL depending on membrane potential; 5. Check possible ATL action on closed NMDAR channels; 6. Analyze trapping block effect on NMDAR channels by ATL. An electrophysiological patch-clamp method to study the effects of ATL on NMDAR currents and calcium imaging to record intracellular calcium responses of primary cortex culture in vitro were used. As a result, the effects of ATL concentrations on NMDAR currents depending on the membrane potential were compared, significant influence of extracellular calcium on NMDAR currents by ATL was revealed, parameters of the open-channel block were determined. It was found that ATL has not been affected on the closed channel and was being a blocker of the open NMDAR channel (it was shown as a "partial trap"), blocking parameters were similar to clinically significant blockers. The data obtained are important for understanding the biophysical properties of NMDAR, as well as clinically important for expanding the understanding of the antidepressants effects on human CNS.