Reversal of diazepam withdrawal induced hyperactivity in mice by BR 16-A (Mentat), a herbal preparation

Abrupt cessation of chronic treatment of diazepam (20 mg/kg/day for 21 days) produced withdrawal reactions. BR 16-A, a multicomponent herbal preparation shown to reverse the withdrawal reactions to opiates was studied against diazepam induced withdrawal reactions in mice. Acute dose of diazepam (20 mg/kg) produced a decrease in the ambulatory and total activity. However, chronic administration for 21 days produced tolerance and no significant change in the ambulatory and total activity. On abrupt termination of diazepam treatment after 21 days, the animals showed anxiety and excitement as there was an increase in ambulatory and total activity. The withdrawal excitement was highest at 72 hr of the last dose of diazepam. Concomittant administration of BR 16-A (100 and 500 mg/kg) reversed the acute effect of diazepam in a dose dependent manner. Similarly, chronic administration of BR 16-A (100 and 500 mg/kg/day for 21 days) with diazepam (20 mg/kg/day for 21 days) also reversed the withdrawal induced hyperambulation and total activity. Chronic administration of BR 16-A per se had no significant effect on the ambulatory and total activity, however, in acute doses, BR 16-A (100 and 500 mg/kg) produced a dose dependent increase in the ambulatory and total activity. BR 16-A with its CNS profile of activity could be a useful preparation in the management of substances of abuse.