Is Receptor Heterogeneity Relevant to the Anxiolytic Actions of Benzodiazepine Receptor Ligands?
The presence of saturable, stereoselective recognition sites for benzodiazepines (BDZ) in the central nervous system (Squires and Braestrup, 1977; Mohler and Okada, 1977) provided the stimulus to synthesize and evaluate potential anxiolytics devoid of the myorelaxant and hypnotic properties associated with ‘classical’ 1,4-BDZ. During the past decade, more than half a dozen chemically distinct (that is, unrelated to 1,4-BDZ) structures have been reported to bind with high affinities to these BDZ receptors (BDZR), with at least as many compounds reported to possess anticonflict (and/or anxiolytic) actions devoid of significant hypnotic and/or myorelaxant potential (reviewed in Skolnick and Paul, 1988). Even so, the mechanism(s) by which a BDZR ligand can effect a selective anxiolytic action has not been well defined either on a molecular or neuroanatomical level. This chapter will critically review the relationship of receptor heterogeneity to the putative ‘anxioselective’ actions of BDZR ligands.
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