Chapter 6. Agents Affecting Appetite

Publisher Summary This chapter discusses studies that focus on agents that affect appetite. In animals, fenfluramine was shown to be slightly less potent as an anorectic than d-amphetamine but with a longer duration of action. Its effect on the central nervous system (CNS) was studied and its activities included (1) decreased confinement motor activity in rats and decreased spontaneous motor activity in mice, (2) prolongation of pentobarbital sleep time in mice, and (3) diminution of hyperactivity caused by amphetamine. Fenfluramine was reported to antagonize the toxicity of amphetamine in aggregated mice but not in isolated mice and was also capable of reducing isolation-induced aggressive behavior. Biochemical studies revealed that fenfluramine decreased the content of norepinephrine and dopamine in mouse and rat brain and pretreatment with a monoamine oxidase inhibitor reversed the effect of fenfluramine from decreasing to increasing motor activity. Additional reports indicated that fenfluramine and amphetamine differ in the mechanism by which they release norepinephrine from the brain. Several investigators reported that fenfluramine caused depletion of 5-hydroxytryptamine in rat brain. A group of long-acting o-aminoalkylbenzhydrols was also reported that had moderate anorexic potency with little stimulation, whose pharmacological profile and structure-activity relationships suggested a mechanism of action different from amphetamine.