Fluoxetine modulates norepinephrine contractile effect on rat vas deferens

The aim of this study was to evaluate whether the antidepressant drug fluox etine could modify rat vas deferens response to norepinephrine (NE), and to compare its effect with that of desipramine and cocaine. Results showed th at 10(-5) M fluoxetine produced a super-sensibility of vas deferens to NE. This result was the same as those obtained for 10(-6) M desipramine or coca ine. Since the effect was Na+- and Cl--dependent, an inhibitory mechanism o f neuronal NE transport was suggested. Fluoxetine did not modify [H-3]prazo sin K-d or B-max in rat vas deferens, reinforcing the hypothesis of a pre-s ynaptic site of action. On the other hand fluoxetine inhibited NE maximal e ffect. This inhibitory effect could be related to an antagonism of calcium entry through the voltage-dependent calcium channel, since it was partially reverted by increasing calcium concentration and, besides, the drug was ab le to inhibit the calcium concentration-response curve also. Contractions i nduced by 5-hydroxytryptamine (5-HT) were not modified in the presence of f luoxetine. It is concluded that fluoxetine modulates rat vas deferens respo nse to low NE concentrations in the same manner as the selective inhibitor of NE neuronal uptake desipramine. This peripheral effect could participate in the modulation of the male reproductive tract observed by these drugs w hen used in clinical trials. (C) 2000 Academic Press.