The action of dexfenfluramine hydrochloride in treating obesity is primarily via decreased caloric intake associated with increased serotonin levels in brain synapses.
Dexfenfluramine hydrochloride is a serotonin reuptake inhibitor and releasing agent.
In vitro studies have confirmed the dual serotoninergic mechanism of action of dexfenfluramine by demonstrating that the drug inhibits serotonin reuptake by axon terminals and causes the release of serotonin from synaptosomes. In animals, the reduced caloric intake and the loss in body weight elicited by dexfenfluramine is associated with release of serotonin from presynaptic axon terminals in the brain, inhibition of neuronal serotonin reuptake, and therefore, an increase of serotonin receptor activation. This results in an enhancement of serotoninergic transmission in the centers of feeding behavior, located in the ventro-medial nucleus of the hypothalamus. In rats, enhanced serotoninergic transmission induced by dexfenfluramine selectively suppressed appetite for carbohydrates which resulted in reduction of food consumption when the dietary carbohydrate to protein ratio was high. In clinical trials, dexfenfluramine treatment in conjunction with a reduced-calorie diet is associated with a reduction in appetite and may slow gastric emptying.