Suriclone: a new cyclopyrrolone derivative recognizing receptors labeled by benzodiazepines in rat hippocampus and cerebellum.
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.
D000818:Animals; D001667:Binding, Competitive; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006358:Hot Temperature; D007700:Kinetics; D008297:Male; D009287:Naphthyridines; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013457:Sulfur Compounds; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D009287:Naphthyridines; D010879:Piperazines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D013457:Sulfur Compounds; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; C037283:suriclone