Nature of functional tolerance produced by chronic flurazepam treatment in the cat

Cats were treated once daily for 35 days with flurazepam (FZP). Different groups received 2, 5 or 20 mg/kg per day. A fourth group was started at 20 mg/kg per day, then the dose was increased to 30, and finally 40 mg/kg per day. Muscle relaxation, ataxia, and other measures of neurological impairment were used to measure drug actions. Tolerance developed rapidly, and no FZP effects were seen after 2-3 weeks of treatment with 2 or 5 mg/kg. Doses of 2-100 mg/kg FZP were injected i.p., 48 h after the last dose of chronic treatment with 2 or 5 mg/kg, and peak FZP effects were recorded. There was an approximate 10-fold shift to the right of the dose-response curve, indicating a large degree of functional tolerance after 5 weeks of FZP treatment. The pattern of tolerance, as measured by dose-response analysis, suggests that it may be different from the functional tolerance developed during barbiturate administration.