Studies on the activity of selected highly lipophilic compounds towards hGAT1 inhibition. Part II.

In the manuscript we describe the latest results involving molecular modeling and pharmacodynamic studies of the selected highly lipophilic compounds acting by human GABA transporter 1 (hGAT1) inhibition. The chemical interaction of seventeen GABA analogues with a model of hGAT1 is described using the molecular docking method. The biological role of GAT1 is related to the regulation of GABA level in the central nervous system and GAT1 inhibition plays an important role in the control of seizure threshold. To confirm that GAT1 can be also a molecular target for drugs used to treat other neurological and psychiatric diseases (e.g. pain and anxiety), in the in vivo part of this study potential antinociceptive and anxiolytic-like properties of tiagabine, a selective GAT1 inhibitor, are described.