Chronic treatment with Ro 15-1788 distinguishes between its benzodiazepine antagonist, agonist and inverse agonist properties

✍ Scribed by Sandra E. File; J. Dingemanse; H. L. Friedman; D. J. Greenblatt

• Publisher: Springer
• Year: 1986
• Tongue: English
• Weight: 570 KB
• Volume: 89
• Category: Article
• ISSN: 0033-3158
• DOI: 10.1007/bf00175201

✦ Synopsis

Ro 15-1788 (fiumazepil)

is an imidazodiazepine that is able to antagonise most of the behavioural actions of the benzodiazepines, as well as having some intrinsic effects. Acute administration of Ro 15-1788 (10 mg/kg) decreases social interaction between male rats and elevates exploratory head-dipping. After 5 days of pretreatment there was tolerance to the former effect, although Ro 15-1788 retained its ability to antagonise the effects on social interaction of the p-carboline, FG 7142. Ro 15-1788 also retained its ability to elevate head-dipping: additionally, the chronically-treated rats had elevated motor activity and rearing scores. The acute effects of lorazepam in the holeboard were unchanged by chronic pretreatment with Ro-15-1788. The plasma and brain concentrations after acute administration of lorazepam were unchanged following chronic administration of Ro 15-1788. After chronic treatment the brain concentrations of Ro 15-1788 were unchanged. It is unlikely that pharmacokinetic factors could underlie the different behavioural changes following chronic treatment.