[Anxiety receptors: new pharmacological approach (author's transl)].

Abstract

The various clinical effects of benzodiazepines have been attributed to the presence of saturable binding sites, stereospecific and of high affinity in the central nervous system. Good correlations have been described between the inhibition of the binding of [3H]diazepam and the anticonvulsant and anticonflictual properties of benzodiazepines. Such results would suggest that these binding sites are the pharmacological receptors responsible for the therapeutic properties of benzodiazepines. In addition, the neuromediator which has been associated with benzodiazepines in terms of its functions is GABA. Up to the present, the anticonvulsant and anticonflictual properties of substances acting on benzodiazepine receptors could not apparently be dissociated. However, b using quinoline derivatives we have been able to dissociate anticonflictual and anticonvulsant properties for substances acting upon benzodiazepine receptors. These substances (PK 8165 and PK 9084) displace diazepam from binding sites (Ki of 100 to 400 nM) in the brain but not peripherally. The fact that PK 9084 and PK 8165 are more active on benzodiazepine derivatives in the presence of anions suggests that they act upon receptors coupled with a chloride ionophore-like. Benzodiazepines, PK 8165 and PK 9084 have anticonflictual properties but cause neither ataxia nor sedation even at doses 5 to 20 times greater than anticonflictual doses. Furthermore, these compounds are not anticonvulsant. In contrast to benzodiazepines, PK 8165 and PK 9084 do not decrease the cGMP of the Purkinje cells of the cerebellum. This cGMP pool being the reflection of the activation of GABAergic receptors, it would seem that these substances must act on a sub-unit of benzodiazepine receptors not coupled with GABA but associated with the chloride ionophore. This sub-unit could be responsible for the anticonflictual properties of substances acting upon benzodiazepine receptors.

• Authors: G Le Fur
• Journal: L'Encephale (Encephale) Vol. 8 Issue 2 Pg. 145-50 ( 1982) ISSN: 0013-7006 [Print] France
• Vernacular Title: Récepteurs de l'anxiété: nouvelle approche pharmacologique.
• PMID: 6125375 (Publication Type: English Abstract, Journal Article)

Chemical References

• Anti-Anxiety Agents
• Chlorides
• Quinolines
• Receptors, Cell Surface
• Receptors, Drug
• Receptors, GABA-A
• gamma-Aminobutyric Acid
• Chlordiazepoxide
• PK 9084
• pipequaline
• Diazepam

Topics

• Animals
• Anti-Anxiety Agents (metabolism)
• Anxiety Disorders (drug therapy, metabolism)
• Binding, Competitive (drug effects)
• Brain (metabolism)
• Chlordiazepoxide (metabolism)
• Chlorides (metabolism)
• Diazepam (metabolism)
• Humans
• Quinolines (metabolism)
• Receptors, Cell Surface (metabolism)
• Receptors, Drug (drug effects, metabolism)
• Receptors, GABA-A
• Seizures (metabolism)
• gamma-Aminobutyric Acid (metabolism)