Brain receptors and zopiclone.

Abstract:

:Zopiclone (ZPC; RP 27,267), which is chemically unrelated to benzodiazepines (BZD), was found to have a similar pharmacological profile and to possess in man hypnotic activity similar to that of some BZD such as nitrazepam. It was, therefore, interesting to study the interaction of ZPC with rat brain receptors and specially with the so-called 'BZD receptors'. ZPC possesses in three rat brain regions a high affinity for BZD receptors: its Ki values measured against [3H]-flunitrazepam are 24 nM in the cerebral cortex, 31 nM in the cerebellum, and 36 nM in the hippocampus. No other brain receptors such as gamma-aminobutyric acid receptor, dopamine receptor, serotonin and noradrenergic receptors are reached by ZPC. Moreover, ZPC seems to bind only to brain BZD receptors and, contrarily to some BZD such as flunitrazepam, it does not reach the peripheral renal BZD-binding sites. The synthesis of [3H]-ZPC has permitted a more in-depth study of the interaction of ZPC with brain receptors. The high affinity of ZPC has been confirmed by equilibrium-binding studies (KD = 13 +/- 4 nM in rat hippocampus) and the study of the modulating effect of gamma-aminobutyric acid and barbiturates on ZPC binding has revealed some differences between ZPC and BZD. It could, therefore, be postulated that ZPC might bind in rat brain to sites which do not correspond exactly to BZD sites.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Blanchard JC,Boireau A,Julou L

doi

10.1159/000137912

subject

Has Abstract

pub_date

1983-01-01 00:00:00

pages

59-69

eissn

0031-7012

issn

1423-0313

journal_volume

27 Suppl 2

pub_type

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