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Information × Registration Number 0220U104447, 0119U001636 , R & D reports Title Neurochemical profiling and brain imaging of a novel neuroprotective compound class, positive allosteric modulators of Sigma-1 receptor. popup.stage_title Head Borysova Tetiana O., Доктор біологічних наук Registration Date 18-12-2020 Organization Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine popup.description2 The effect of Sig-1 receptor blockade on synaptic transmission was investigated and it was found that the Sig-1R NE-100 antagonist can cause an acute effect at the presynaptic level by modulating the transporter-mediated accumulation of GABA and glutamate, as well as their exocytosis, signals. The two-phase effect of the Sig-1R NE-100 blocker in the concentration range of 1-100 μM was demonstrated. It has been shown that the effects of NE-100 can develop with the participation of GABA-A and GABA-B receptors, as their antagonists prevented an increase in the accumulation of [3H]GABA caused by NE-100 in the concentration range of 1-10 μM. It was shown that the accumulation of L-[14C]glutamate decreased under the influence of NE-100 at concentrations of 10 - 100 μM. It has been suggested that the reduction in the accumulation of both neurotransmitters under the influence of NE-100 may be due to antagonist-induced membrane depolarization. The tonic release of [3H]GABA measured in the presence of NO-711 was not changed by the antagonist, suggesting that NE-100 did not disrupt membrane integrity. NE-100 (10-100 μM) was shown to reduce the release of L-[14C]glutamate and [3H]GABA by exocytosis caused by potassium depolarization and was shown to be associated with NE-100-induced dysfunction of potential-dependent Ca2+ channels. NE-100 reduced the transporter-mediated release of L-[14C]glutamate induced by potassium depolarization and the FCCP protonophore, which underlies the neuroprotective action of the antagonist in hypoxia / ischemia. The revealed lack of toxicity and the ability to inhibit the functioning of GABA transporters indicate in favor of the high potential of the allosteric modulator Sig-1 receptor E1R synthesized by the Latvian group as an effective drug.  Product Description popup.authors Dudarenko Marina V Krisanova Natalia V. Paliienko Konstantin O. Panas Ihor D. Pastukhov Artem O. Pozdnyakova Natalia H. popup.nrat_date 2020-12-18 Close