Tofizopam modulates the affinity of benzodiazepine receptors in the rat brain.

Tofizopam, a 3,4-benzodiazepine, lacks the sedative action common to 1,4-benzodiazepines, but has anxiolytic activity. In this study we administered tofizopam (50 mg/kg) to rats perorally twice a day for six days, and analyzed the binding of [3H]flunitrazepam to benzodiazepine receptors of these drug-treated rats. The effect of tofizopam treatment was compared to that brought about by treatment with diazepam (12 mg/kg twice a day for six days) and to binding in controls treated with vehicle. Compared to the controls, the diazepam group had a marked decrease in binding of [3H]flunitrazepam to benzodiazepine receptors both in the forebrain and in the hindbrain. As a result of the increased affinity of the receptors tofizopam slightly, but statistically significantly, enhanced binding. With both drugs the number of receptors was unaltered. The effect of tofizopam in the hindbrain was similar to that in the forebrain. The results of this study support our earlier finding from single-dose studies that tofizopam acts indirectly on benzodiazepine receptors.