Lack of interaction between flibanserin and antidepressants in inducing serotonergic syndrome in rats.
This study was aimed at evaluating the ability of flibanserin, a 5-HT1A receptor full agonist with antidepressant potential, to induce the 5-HT syndrome (flat body posture, hindlimb abduction and forepaw treading) in rats previously administered with clinically active antidepressants imipramine, fluoxetine or paroxetine. The 5-HT syndrome was observed for 50 min after intraperitoneal administration of flibanserin (0, 8 or 64 mg/kg) given 10 min after antidepressants (0 or 15 mg/kg). Flibanserin induced flat body posture and very slight hindlimb abduction only at 64 mg/kg. No dose of flibanserin elicited forepaw treading. Similar but milder symptoms were induced by antidepressants. No interaction between flibanserin and antidepressants was observed. A dose of 10 mg/kg flibanserin did not change the flat body posture induced by 8 mg/kg (+/-)-8-OH-DPAT but antagonized (+/-)-8-OH-DPAT-induced forepaw treading.
Borsini
F
F
Boehringer Ingelheim Pharma KG, CNS Department, Building J63, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany. Franco.Borsini@bc.boehringer-ingelheim.com
Brambilla
A
A
Cesana
R
R
Grippa
N
N
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D017374:Paroxetine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D020230:Serotonin Syndrome / Q000139:chemically induced*
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D001562:Benzimidazoles; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; C098107:flibanserin; D017374:Paroxetine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007099:Imipramine