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.

[1]  F. Borsini,et al.  Effect of flibanserin (BIMT 17), fluoxetine, 8-OH-DPAT and buspirone on serotonin synthesis in rat brain , 1999, European Neuropsychopharmacology.

[2]  P. Gillman Serotonin syndrome: history and risk , 1998, Fundamental & clinical pharmacology.

[3]  C. Montigny,et al.  In vivo electrophysiological assessment of the agonistic properties of flibanserin at pre‐ and postsynaptic 5‐HT1A receptors in the rat brain , 1998, Synapse.

[4]  L. Seiden,et al.  BIMT 17: a putative antidepressant with a fast onset of action? , 1997, Psychopharmacology.

[5]  M. Kleven,et al.  Pharmacological characterization of in vivo properties of putative mixed 5-HT1A agonist/5-HT(2A/2C) antagonist anxiolytics. II. Drug discrimination and behavioral observation studies in rats. , 1997, The Journal of pharmacology and experimental therapeutics.

[6]  C. Tanner,et al.  Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease , 1997, Neurology.

[7]  K. Inagawa,et al.  Pharmacological profile of (−)HT-9OB, a novel 5-HT1A receptor agonist/5-HT2 receptor antagonist , 1995, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[8]  F. Borsini,et al.  The effect of BIMT 17, a new potential antidepressant, in the forced swimming test in mice , 1995, Behavioural pharmacology.

[9]  I. Martin,et al.  Molecular biology of 5-HT receptors , 1994, Neuropharmacology.

[10]  F. Artigas,et al.  Chronic treatment with fluvoxamine increases extracellular serotonin in frontal cortex but not in raphe nuclei , 1993, Synapse.

[11]  R. Zerbe,et al.  Possible monoamine oxidase inhibitor-serotonin uptake inhibitor interaction: fluoxetine clinical data and preclinical findings. , 1993, Journal of clinical psychopharmacology.

[12]  D. Sibley,et al.  Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. , 1993, The Journal of biological chemistry.

[13]  T. Sharp,et al.  Behavioural evidence for a functional interaction between central 5‐HT2 and 5‐HT1A receptors , 1990, British journal of pharmacology.

[14]  P. Hutson,et al.  Neurochemical and behavioural evidence for an agonist action of 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163) at central 5-HT receptors. , 1987, European journal of pharmacology.

[15]  S. Peroutka,et al.  Differential effects of 5-hydroxytryptamine1A selective drugs on the 5-HT behavioral syndrome , 1986, Pharmacology Biochemistry and Behavior.

[16]  D. Middlemiss,et al.  Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat. , 1985, European journal of pharmacology.

[17]  G. M. Goodwin,et al.  A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5‐HT1 and 5‐HT2 receptors , 1985, British journal of pharmacology.

[18]  G. Ettlinger,et al.  The biochemical, behavioral, and neurologic effects of high L‐tryptophan intake in the Rhesus monkey , 1963, Neurology.

[19]  R. Glennon,et al.  Multiple populations of serotonin receptors may modulate the behavioral effects of serotonergic agents. , 1991, Life sciences.

[20]  M. Tricklebank The behavioural response to 5-HT receptor agonists and subtypes of the central 5-HT receptor , 1985 .