Precipitated withdrawal by a benzodiazepine receptor antagonist (Ro 15-1788) after 7 days of diazepam

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Science  17 Sep 1982:
Vol. 217, Issue 4565, pp. 1161-1163
DOI: 10.1126/science.6287579


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.