Novel Functionalized Amino Acids as Inhibitors of GABA Transporters with Analgesic Activity.

ABSTRACT: Neuropathic pain resistance to pharmacotherapy has encouraged researchers to develop effective therapies for its treatment. γ-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 in

SUBMITTER: Gryzlo B 

PROVIDER: S-EPMC8397297 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature