Chemistry of GABAB receptor ligands: focus on agonists and antagonists

Since the discovery of GABAB receptor by Norman G. Bowery and coworkers in 1980, a striking endeavour was made by industrial and academic researchers to develop GABAB receptor ligands for therapeutic application in a variety of diseases associated with dysfunctions of the gabaergic system. Although baclofen (Lioresal) is still the only approved GABAB receptor agonist, this sustained research effort has produced many new compounds which are able to exert GABAB agonist, partial agonist or antagonist activity. This chapter presents an overview of the outcomes in this field, with a special focus on the chemistry, structure–activity relationship and mechanism of action of several GABA and baclofen analogues, derivatives and bioisosteres. © Springer International Publishing Switzerland 2016.