Fluoxetine modulates norepinephrine contractile effect on rat vas deferens.
The aim of this study was to evaluate whether the antidepressant drug fluoxetine could modify rat vas deferens response to norepinephrine (NE), and to compare its effect with that of desipramine and cocaine. Results showed that 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 cocaine. Since the effect was Na(+)- and Cl(-)-dependent, an inhibitory mechanism of neuronal NE transport was suggested. Fluoxetine did not modify [(3)H]prazosin K(d) or B(max) in rat vas deferens, reinforcing the hypothesis of a pre-synaptic site of action. On the other hand fluoxetine inhibited NE maximal effect. 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 able to inhibit the calcium concentration-response curve also. Contractions induced by 5-hydroxytryptamine (5-HT) were not modified in the presence of fluoxetine. It is concluded that fluoxetine modulates rat vas deferens response 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 when used in clinical trials.
Busch
L
L
Department of Pharmacology, School of Dentistry, University of Buenos Aires, Marcelo T. de Alvear 2142, Buenos Aires, 1122, Argentina.
Wald
M
M
Sterin-Borda
L
L
Borda
E
E
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology
D002118:Calcium; D003042:Cocaine; D003891:Desipramine; D005473:Fluoxetine; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D012965:Sodium Chloride