Publications

Latest publication 08/04/2021

Novel Functionalized Amino Acids as Inhibitors of GABA Transporters with Analges

Neuropathic pain resistance to pharmacotherapy has encouraged researchers to develop effective therapies for its treatment. Gamma-Aminobutyric acid...

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    [title] => Novel Functionalized Amino Acids as Inhibitors of GABA Transporters with Analges
    [paragraph] => Novel Functionalized Amino Acids as Inhibitors of GABA Transporters with Analgesic Activity
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Authors
B Gryzlo, P Zareba, K Malawska et al

 Lab
Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
Journal
ACS Chemical Neuroscience
Abstract
Neuropathic pain resistance to pharmacotherapy has encouraged researchers to develop effective therapies for its treatment. Gamma-Aminobutyric acid (GABA) transporters 1 and 4 (mGAT1 and mGAT4) have been increasingly recognized as promising drug targets for neuropathic pain (NP) associated with imbalances in inhibitory neurotransmission. In this context, we designed and synthesized new functionalized amino acids as inhibitors of GABA uptake and assessed their activities toward all four mouse GAT subtypes (mGAT1–4). According to the obtained results, compounds 2RS,4RS-39c (pIC50 (mGAT4) = 5.36), 50a (pIC50 (mGAT2) = 5.43), and 56a (with moderate subtype selectivity that favored mGAT4, pIC50 (mGAT4) = 5.04) were of particular interest and were therefore evaluated for their cytotoxic and hepatotoxic effects. In a set of in vivo experiments, both compounds 50a and 56a showed antinociceptive properties in three rodent models of NP, namely, chemotherapy-induced neuropathic pain models (the oxaliplatin model and the paclitaxel model) and the diabetic neuropathic pain model induced by streptozotocin; however compound 56a demonstrated predominant activity. Since impaired motor coordination is also observed in neuropathic pain conditions, we have pointed out that none of the test compounds induced motor deficits in the rotarod test.
BIOSEB Instruments Used
Electronic Von Frey 4 (BIO-EVF4),Electronic Von Frey 5 with embedded camera (BIO-EVF5)
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A quick solution to determine the mechanical sensitivity threshold in rodents (mice and rats). Now wireless, to be free from annoying cables!

This precise and easy-to-use electronic instrument is a must-have reference for your research in analgesia, nociception, neuro-pathologies and post-operative pain.

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The EVF5 includes an embedded camera inside the stimulator handle and a new, dedicated software revolutionizing the experimental process.

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