Registration Number
0223U004617,
0120U105018
, R & D reports
Title
Study of excitability of primary nociceptive neurons of the peripheral nervous system: the first year of the project
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Head
Kryshtal Oleh O., Доктор біологічних наук
Registration Date
26-11-2023
Organization
Bogomolets Institute of Physiology of the National Academy of Sciences of Ukraine
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In order to elucidate the role of the cytoskeleton and its transformation in modulating ion channels of excitable cells in the peripheral nervous system, the activity of selected lead compounds was investigated using the ex vivo skin-nerve model. This model enables the measurement of nociceptive signals from individual isolated sensory nerve endings, providing data on the antinociceptive activity of these compounds.
Compound 11401 was identified as having a long-term, stable antinociceptive effect on single fibers, reaching a level of 36%. Electrophysiological studies were conducted on analogues of active compounds using the patch-clamp method in the "whole cell" configuration, focusing on ion channels Nav1.7, TRPV1, TRPV4, and GABA, which play roles in pain transmission and inflammation processes. The investigated compounds exhibited inhibitory effects on Nav 1.7, TRPV1, TRPV4, and GABA channels at a concentration of 100 µM, suggesting potential analgesic (anti-inflammatory) effects.
Experimental models of somatic and visceral peripheral pain, considered adequate for testing the analgesic properties of novel drugs, revealed that compound 1325487222 (the latest synthesized blocker of voltage-dependent Nav1.7 ion channels) exhibited its analgesic effect only 20 minutes after administration. It then reliably maintained an anesthetic effect for at least the last 40 minutes of the study, likely due to its non-selective effect on other receptors of peripheral nociceptive endings. Compound 1325487222 (the latest synthesized GABA receptor blocker) demonstrated a rapid and long-lasting analgesic effect, indicating its potential as a promising new molecule for further research and the development of novel analgesic agents.
Product Description
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Kotyk Olena A.
Maximyuk Olexandr P
Nesterenko Yuliia
Romanov Artur
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2023-11-26
