Additive effects on rat brain 5HT release of combining phentermine with dexfenfluramine.

OBJECTIVE AND

DESIGN

This study examined the effects of the anti-obesity agents, phentermine and dexfenfluramine given alone or in combination, on in vitro and in vivo 5HT release from rat brain tissue.

RESULTS

In vitro, phentermine was without effect on basal [3H]5HT efflux from hypothalamic slices whereas dexfenfluramine (10 microM) evoked a 131% increase in [3H]5HT release. In combination, the two drugs did not alter [3H]5HT release beyond that caused by dexfenfluramine alone. At pharmacologically equivalent doses, phentermine (5.7 mg/kg, i.p.) caused a rapid, modest elevation, and dexfenfluramine (3 mg/kg, i.p.) a larger but equally rapid elevation of extracellular 5HT in the microdialysates from the rat anterior hypothalamus. In combination, the increase in extracellular 5HT evoked by these drugs was not significantly greater than the sum of their individual effects.

CONCLUSIONS

This study provides evidence that phentermine's actions are not restricted to catecholamine systems and indicates that combining phentermine with dexfenfluramine results in an additive increase in neuronal 5HT release.