BLOCKADE OF 5-HYDROXYTRYPTAMINE AND NORADRENALINE UPTAKE BY VENLAFAXINE - A COMPARATIVE-STUDY WITH PAROXETINE AND DESIPRAMINE

1 Venlafaxine is an antidepressant agent which blocks in vitro the reu ptake of both 5-HT and NA. The present in vivo electrophysiological st udies were undertaken, in the rat, to compare the effects of venlafaxi ne on 5-HT and NA reuptake to those of the selective 5-HT reuptake inh ibitor paroxetine and the selective NA reuptake inhibitor desipramine. 2 Administered acutely, venlafaxine dose-dependently prolonged the ti me required for a 50% recovery (RT50) of the firing activity of dorsal hippocampus CA(3) pyramidal neurons from the suppression induced by m icroiontophoretic applications of 5-HT and NA. Venlafaxine and paroxet ine increased with a similar potency the RT50 values for 5-HT, while d esipramine was more potent than venlafaxine at increasing the RT50 val ues for NA. Moreover, venlafaxine demonstrated a greater potency at in creasing the RT50 values for 5-HT compared to that of NA.3 A two-day t reatment with venlafaxine (delivered s.c. by osmotic minipumps) increa sed the RT50 values for both 5-HT and NA applications. The RT50 values for 5-HT were significantly increased at a dose of 10 mg kg(-1) day(- 1), whereas those for NA were increased at a dose of 20 mg kg(-1) day( -1) consistent with the data obtained following the acute administrati on of venlafaxine. 4 Taken together, these results indicate that, in v ivo, venlafaxine blocks both reuptake processes, with a potency greate r for the 5-HT than for the NA reuptake process. This dual action, com bined with the differential potency of venlafaxine, might constitute t he biological substratum responsible for its apparent unique clinical efficacy in major depression.