Novel, highly potent and in vivo active inhibitor of GABA transporter subtype 1 with anticonvulsant, anxiolytic, antidepressant and antinociceptive properties

Therapeutic effects of Jiaotai pill on rat insomnia via regulation of GABA signal pathway

“…The GABA signal pathway performs two functions: synthesis and transport of GABA, and synaptic and non-synaptic release of GABA [14]. The synaptic release of GABA is related to certain proteins such as GAD-65, GAD-67 and GABA-T, which are responsible for converting glutamate to the GABA [15,16]. The transport of GABA neurotransmitter is related to GABA transporters such as GAT-1, GAT-1, GAT-1 and GAT-3, which belong to the solute carrier 6 genes family A (SLC6A) of Na + -dependent transporters [17].…”

MS‐Based Screening of 5‐Substituted Nipecotic Acid Derived Hydrazone Libraries as Ligands of the GABA Transporter 1

“…So far, tiagabine ( 2 ) is the only GAT1‐selective GABA uptake inhibitor in clinical use and it was approved as add‐on treatment of partial‐onset seizures . Furthermore, several experimental GAT1 inhibitors such as SK&F‐89976A ( 3 ), NO711 ( 4 ), and DDPM‐2571 ( 5 ) have been synthesized and characterized with respect to their biological activities including anticonvulsant, anxiolytic, antidepressant, and antinociceptive effects . GAT1‐selective inhibitors are usually derivatives of small cyclic amino acids, particularly nipecotic acid ( 6 ) or guvacine ( 7 ).…”

“…These small cyclic amino acids, 6 and 7 , already possess reasonable inhibitory potency toward GAT1 in vitro, but due to their polarity they have limited blood–brain barrier permeability and display hardly any anticonvulsant effects in vivo . The substitution of the amino group of the cyclic amino acids 6 or 7 with a spacer and an aromatic residue is a common approach to increase lipophilicity and to improve the capability of crossing the blood–brain barrier and thus to obtain compounds such as 2 – 5 that mediate potent anticonvulsant effects in vivo …”

Insights into the interaction mechanism between tiagabine hydrochloride and two serum albumins

“…1) is a classical anticonvulsive drug used for treating epileptics in clinics, and is widely used in the United States, Europe and other countries. 1,2 It selectively increased the concentration of g-aminobutyric acid in presynaptic neurons and glial cells for effective therapy. Besides, it has been utilized to treat anxiety disorders, panic disorders, posttraumatic stress disorders, as well as neuropathic pain.…”