Some properties of brain specific benzodiazepine receptors: New evidence for multiple receptors

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

“…However, these compounds have come under critical review because of the problems of drug dependence, tolerance, suppression of rapid eye movement sleep, rebound insomnia, and amnesia (Lader, 1994;Woods and Winger, 1995). Benzodiazepines produce their pharmacological effects by allosterically and positively modulating the action of GABA at GABA A receptors at specific ionotropic sites (Squires et al, 1979). Over the last two decades, a search has been undertaken for compounds chemically unrelated to benzodiazepines that may produce fewer unwanted effects but retain therapeutic properties.…”

The benzodiazepines: recent trends

“…However, work by Squires et al (1979) indicated that the triazolopyridazine CL 218872 (see Fig. 1) was able to displace diazepam from its binding sites in…”

“…The further claim (not since confirmed) that this compound produced anxiolytic and anti-convulsant effects but little sedation aroused intense interest, the hypothesis being that one of the receptor subtypes was responsible for the sedative effects of the benzodiazepines, while the other mediated the anxiolytic and anti-convulsant actions. Further support was added to the multiple site hypothesis by studies on the thermal inactivation of benzodiazepine receptors, the stability of which could not be adequately explained by the assumption that only a single homogeneous population of receptors existed (Squires et al 1979).…”

Comparison of Typical and Atypical Benzodiazepines on the Central and Peripheral Benzodiazepine Receptors

“…Recently, several papers have described the existence of multiple BZ receptors (5)(6)(7)(8). Furthermore, the distribution of BZ receptor subtypes in the central nervous system (CNS) is heterogeneous and the proportion of BZ receptor subtypes does differentially localize in some brain regions (see 9).…”

“…This heterogeneity in distribution may explain the multiple BZ pharmacological effects. For example, the triazolopyridazine CL 218,872 has a preferential affinity for the so-called BZ type 1 receptors in vitro and also may possess antianxiety properties with little sedation (5,9,10). This drug has also higher affinity binding sites in the cerebellum than in the cortex (3,8,9 did not demonstrate any significant differ ences.…”