Long-term treatment with fluoxetine associates with peripheral effects on rat vas deferens contractility.
The aim of this work was to study whether long-term treatment with fluoxetine could induce peripheral effects by modifying vas deferens contractile activity. For this purpose the contractile response to NE, and 5-HT of vas deferens isolated from male Wistar rats that received fluoxetine 10 mg/kg/day i.p., during 21 days, was studied using the isolated organ bath technique. Results show that vas deferens of treated rats presented spontaneous activity, an effect that was abolished by prazosin and isoproterenol and that was not affected by nitroprusside or indomethacin. In addition, fluoxetine did not modify the response to calcium suggesting that spontaneous activity was not a consequence of an abnormal calcium movement. Fluoxetine induced a significant increase in the response of vas deferens to 5-HT and to low NE concentrations while NE maximal effect was unaffected. Fluoxetine treatment did not modify the binding parameters of [3H]-prazosin to vas deferens. It is concluded that long-term treatment with fluoxetine modifies vas deferens contractile activity. This effect could be the result of an alteration of adrenergic neurotransmission and could account for some of the untoward effects observed during clinical course with fluoxetine.
Busch
L
L
Department of Pharmacology, School of Dentistry, University of Buenos Aires, Argentina. lucila@farmaco.odon.uba.ar
Wald
M
M
Borda
E
E
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005473:Fluoxetine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
D018663:Adrenergic Agents; D018687:Antidepressive Agents, Second-Generation; D016861:Cyclooxygenase Inhibitors; D012702:Serotonin Antagonists; D005473:Fluoxetine; D009599:Nitroprusside; D012701:Serotonin; D007650:Ketanserin; D014700:Verapamil; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin; D007213:Indomethacin