Abstract
Drug discrimination is a reliable, sensitive, and pharmacologically specific behavioral procedure for studying the mechanism of action of drugs. These qualities have enabled investigators to classify and differentiate closely related compounds and gather important information concerning their mechanism(s) of action in vivo. Although drugs from various pharmacological classes have been used to establish discriminative stimulus control, the focus of this chapter is on how drug discrimination procedures have been used to study the in vivo pharmacology of GABAB receptor ligands. More specifically, we will review several different drug discrimination procedures and discuss how they have been used to qualitatively and quantitatively study different components of a drug with a relatively simple mechanism of action (baclofen) and a drug with a more complex mechanism of action [gamma-hydroxybutyrate (GHB)]. A number of studies have provided evidence that the behavioral effects of baclofen and GHB are mediated predominantly by GABAB receptors; however, there is growing evidence that the mechanisms mediating the effects of these two drugs are not identical. The differences between baclofen and GHB are relevant not only for understanding their distinct therapeutic and abuse-related effects, but also for understanding their susceptibility to positive modulatory effects, which could allow for a more selective modulation of the GABAB receptor system, thereby leading to safer and more effective therapeutics.
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Drs. Baladi and Carter are employed by Jazz Pharmaceuticals and have received stock awards and stock options exercisable for ordinary shares of Jazz Pharmaceuticals plc.
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Baladi, M.G., Carter, L.P. (2016). Drug Discrimination Studies for Investigations on the Mechanisms of Action of GABAB Receptor Ligands. In: Colombo, G. (eds) GABAB Receptor. The Receptors, vol 29. Humana Press, Cham. https://doi.org/10.1007/978-3-319-46044-4_9
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