Effect of fenfluramine on sympathetic firing rate

The effects of acute and chronic treatment with fenfluramine have been explored in two experiments. Three and twenty-four hours following the injection of fenfluramine 20 mg/kg the firing rate of sympathetic efferent nerves to brown adipose tissue was significantly increased compared to sham injected controls. Body weight loss following acute treatment with fenfluramine was significantly greater at three and twenty-four hours than in the vehicle-treated controls. In the chronic experiment animals were treated once daily for 12 days with 20 mg/kg of fenfluramine. There were two control groups. One control group ate ad lib and a second control group was pair fed to maintain body weight comparable to that of the fenfluramine-treated animals. By the twelfth day food intake in the fenfluramine-treated animals had returned to control levels. Sympathetic firing rate after three days of treatment with fenfluramine was significantly higher in the treated animals than in ad lib fed controls. The ad lib fed controls were likewise significantly higher than the vehicle-treated, pair-gained controls. After 12 days of treatment fenfluramine treated animals had sympathetic firing rates which were still slightly but significantly higher than those of the vehicle-treated controls whereas the vehicle-treated, pair-gained animals had a small but significantly reduced firing rate. These data support the hypothesis that fenfluramine can increase peripheral sympathetic activity.