Changes in benzodiazepine receptors of rat brain after long-term treatment with the Ca(2+)-antagonists nifedipine, verapamil, flunarizine and with the calmodulin antagonist trifluoperazine.

1. The binding of [3H]flunitrazepam to benzodiazepine receptors in the cerebral cortex and hippocampus (membrane fraction P2) was studied after 13-day oral treatment of male Wistar rats with the Ca(2+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin (CaM)-antagonist trifluoperazine (TFP) (3 mg/kg). 2. The changes in the binding characteristics of the benzodiazepine receptors in the frontal cortex were studied in vitro after the addition of nifedipine (10(-6) and 10(-5) M) and verapamil (10(-6) and 10(-5) M). 3. A significant decrease of the binding capacity (Bmax) of [3H]flunitrazepam was established after in vivo treatment with the three Ca(2+)-antagonists as well as after TFP, the decrease being much more pronounced in the hippocampus. 4. Changes in the affinity values (Kd) of [3H]flunitrazepam binding were found in neither of the groups. 5. No data for a direct interaction of nifedipine and verapamil with the brain benzodiazepine receptors were obtained in in vitro experiments.