Model
Digital Document
Publisher
Florida Atlantic University
Description
Dysfunction of GABAB-receptor (GABAB-R)-mediated synaptic transmission underlies various nervous system disorders including epilepsy, depression, schizophrenia, and addiction. Currently, only one GABAB-R orthosteric ligand is in clinical use. However, side effects such as sedation, tolerance, and motor impairment limit its use. A dissociation of the therapeutic effects from the side effects may be achievable with drugs enhancing the endogenous physiological cellular response. The development of GABAB-R allosteric modulators has provided new modes of efficacy that may facilitate the development of novel therapeutic agents. In the present study, we investigated the effects of novel, newly synthesized GABAB-R allosteric ligands using a HEK-293 cell line stably expressing human GABAB1(b)/human GABAB(2) subunits using a cell-based cAMP HTRF assay. One compound was identified and characterized as a potential novel GABAB-R positive allosteric modulator (PAM), and will be subjected to further in vitro and in vivo analyses.
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