Precipitated Withdrawal by a Benzodiazepine Receptor Antagonist (Ro 15-1788) After 7 Days of Diazepam

Abstract

Baboons implanted with intragastric catheters were given diazepam (10 milligrams per kilogram of body weight) twice daily for 45 consecutive days. On days 7 and 35, they were given intramuscular injections of the benzodiazepine receptor antagonist Ro 15-1788. Mild and intermediate withdrawal signs, including retching and vomiting, were observed after 7 days of diazepam, and more frequent and intense withdrawal signs, including tremor and convulsion, occurred after 35 days of diazepam. With the termination of the diazepam injections after 45 days, a mild to intermediate withdrawal syndrome was observed over the next 15-day period.