Suriclone: A New Cyclopyrrolone Derivative Recognizing Receptors Labeled by Benzodiazepines in Rat Hippocampus and Cerebellum

Abstract

Suriclone (RP 31,264), like zopiclone (RP 27,267), belongs to the family of cyclopyrrolones and is chemically entirely different from the benzodiazepines (BZDs). However, it possesses a pharmacological profile close to that of the BZDs and proved to be useful in therapeutics as an anxiolytic agent. In the present paper it is shown that suriclone possesses a high affinity for flunitrazepam binding sites and that tritiated suriclone binds specifically with high affinity in rat hippocampus (KD = 0.44 +/- 0.03 nM) and rat cerebellum (KD = 0.53 +/- 0.12 nM). Further, suriclone binding sites are recognized by BZDs or zopiclone, similarly in the two regions. The affinities of four BZD derivatives--nitrazepam, flunitrazepam, diazepam, and chlordiazepoxide--are similar for suriclone and flunitrazepam binding sites. Suriclone binding sites are, like flunitrazepam sites, protected from thermal inactivation by gamma-aminobutyric acid (GABA) (10 microM), but only flunitrazepam binding is enhanced by GABA. It could be postulated from this that suriclone interacts with a subpopulation of receptors that might be modulated differently from flunitrazepam binding sites. Our results indicate that suriclone could be a new probe for investigating the so-called BZD receptors.

Behavioral analysis of zopiclone on the basis of their discriminative stimulus properties in the rat.

“…This may be the reason why suriclone did not generalize completely to the zopiclone stimuli. Zopiclone binds to benzo diazepine receptors, and its affinity is com parable to those of diazepam and nitrazepam (8,19). In the present studies, diazepam, nitrazepam and alprazolam were also general ized to the zopiclone stimulus.…”

Pharmacologic characterization of a novel non-benzodiazepine selective anxiolytic, DN-2327.

“…By contrast, DN 2327 was more potent and longer lasting than diazepam in its ability to protect against the effects of pentylenetetrazol. CGS9896 (17) and suriclone (18) have been reported to possess good separation ratios between their anxiolytic and muscle-relaxant actions, and it has also been shown that these two com pounds have a more potent protective effect against pentylenetetrazol-induced convulsion than against bicuculline or picrotoxin induced convulsion. In the neurochemical study, DN-2327 showed a more potent af finity for benzodiazepine receptors than did diazepam.…”

Pharmacological Characterisation of a Modified Social Interaction Model of Anxiety in the Rat

“…A wide range of psy choactive drugs has, therefore, been investigated includ ing classical benzodiazepines and non-benzodiazepine compounds which displace benzodiazepines from their binding sites on brain membranes. Of these, suriclone (a benzodiazepine-like cyclopyrrolone) [11] has anxiolytic activity [12], but has the full profile of activities of clas sical benzodiazepines [13], whilst CL 218872 [14,25] and premazepam [15] have anxiolytic, but less musclerelaxant and/or sedative properties. In addition, the an xiolytics buspirone [16] and sodium valproate (which is active in other models of anxiety) [17][18][19] do not dis place central benzodiazepine binding and have also been tested.…”