Periodic benzodiazepine antagonist administration prevents benzodiazepine withdrawal symptoms in primates.
Daily administration of diazepam (1.5 or 6 mg/kg) in Rhesus monkeys results in the progressive development of physical dependence, as evidenced by Ro15-1788 (5 mg/kg i.m.) precipitated withdrawal symptoms including retching, vomiting, face and limb tremors. Every third day administration of the benzodiazepine antagonist, Ro15-1788, during a similar period of continuous diazepam exposure, significantly decreases withdrawal behaviors. During the course of diazepam exposure (with or without periodic Ro15-1788 administration) effects of chronic diazepam on spontaneously elicited sedative and active behaviors were not altered. It is postulated that physical dependence reverts to a drug naive state after each exposure to the benzodiazepine antagonist. This treatment may represent a possible therapeutic approach for preventing the (time dependent) development of physical dependence and the accompanying severe withdrawal symptoms.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003975:Diazepam / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004334:Drug Administration Schedule; D005442:Flumazenil / Q000008:administration & dosage*; D008253:Macaca mulatta; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000517:prevention & control*
D005442:Flumazenil; D003975:Diazepam