Antagonism of flurazepam and other effects of Ro15-1788, PK8165 and Ro5-4864 on the GABA-A receptor complex in rat cuneate nucleus.

Article date: 1985/10/29

PubMed ID: 3002803

Journal name: European journal of pharmacology (ISSN: 0014-2999)


In slices of rat cuneate nucleus, responses to the GABA-A receptor agonist muscimol were potentiated by flurazepam. The maximal potentiation by 1 microM flurazepam was antagonized by the neuronal benzodiazepine receptor ligand Ro15-1788 3 microM, by the quinoline derivative PK8165 0.1 microM and by the peripheral-type benzodiazepine receptor ligand Ro5-4864 0.1 microM. Another ligand for the peripheral-type benzodiazepine receptor, PK11195 10 microM, enhanced the potentiating effect of a submaximal concentration of flurazepam 0.1 microM and prevented the antagonism of flurazepam by Ro5-4864. At much higher concentrations of these drugs, additional effects were seen. Ro15-1788 30 microM and PK11195 30 microM each caused small potentiations of muscimol while Ro5-4864 30 microM caused a small antagonism. Ro15-1788 30 microM, PK8165 100 microM and Ro5-4864 30 microM all antagonized the potentiation of muscimol by pentobarbitone 10 microM; also, PK8165 and Ro5-4864 enhanced the potency of picrotoxin as an antagonist of muscimol. It is concluded that both Ro5-4864 and PK8165 have several distinct effects on the GABA-A receptor complex, all of which could result in reduced responses to muscimol.

This document is available from: http://directlinks.cc/files/muscimol/3002803.pdf

Author List: Simmonds M A

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Anticonvulsants; Benzodiazepinones; Quinolines; Receptors, GABA-A; Picrotoxin; Muscimol; 4'-chlorodiazepam; Flumazenil; Pentobarbital; Flurazepam; pipequaline;

Mesh terms: Animals; Anticonvulsants/pharmacology; Benzodiazepinones/pharmacology; Drug Synergism; Flumazenil; Flurazepam/antagonists & inhibitors; In Vitro Techniques; Male; Medulla Oblongata/drug effects; Muscimol; Pentobarbital/pharmacology; Picrotoxin/pharmacology; Quinolines/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/drug effects;

3002803.txt ยท Last modified: 2018/11/22 21:16 (external edit)