Effect of flibanserin (BIMT 17), fluoxetine, 8-OH-DPAT and buspirone on serotonin synthesis in rat brain

@article{Brambilla1999EffectOF,
  title={Effect of flibanserin (BIMT 17), fluoxetine, 8-OH-DPAT and buspirone on serotonin synthesis in rat brain},
  author={Alessandro Brambilla and A. Baschirotto and N Grippa and Franco Borsini},
  journal={European Neuropsychopharmacology},
  year={1999},
  volume={10},
  pages={63-67}
}

Pharmacology of flibanserin.

Flibanserin displays antidepressant-like activity in most animal models sensitive to antidepressants and does not display consistent effects in animal models of anxiety and seems to exert potential antipsychotic effects.

Flibanserin, a potential antidepressant drug, lowers 5‐HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5‐HT1A receptors

The results show that the stimulation of 5‐ HT1A receptors plays a major role in the effect of flibanserin on brain extracellular 5‐HT, DA and NA.

Flibanserin and 8-OH-DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair-bond quality.

While 8-OH-DPAT-treated female marmoset monkeys display decreased sexual receptivity and increased aggressive interactions with their male pairmates, flibanserin-treatedFemale marmosets demonstrate increased affiliative behavior with theirmale pairmates.

Lack of interaction between flibanserin and antidepressants in inducing serotonergic syndrome in rats.

Flibanserin induced flat body posture and very slight hindlimb abduction only at 64 mg/kg and antagonized (+/-)-8-OH-DPAT-induced forepaw treading, and similar but milder symptoms were induced by antidepressants.

Effect of the β3 adrenoceptor agonist CL 316243 on hypothalamic 5-HT synthesis and suppression of REM sleep in the rat

The present observations suggest that acute administration of CL 316243 causes antidepressant-like effects on REM sleep, possibly mediated by increased central 5-HT synthesis, however, these effects are not maintained with repeated dosing.

Flibanserin, a drug intended for treatment of hypoactive sexual desire disorder in pre-menopausal women, affects spontaneous motor activity and brain neurochemistry in female rats

The present study indicates that flibanserin is able to modulate dopaminergic and serotonergic activity in distinct brain areas and may contribute to its therapeutic efficacy in HSDD.

Multifunctional pharmacology of flibanserin: possible mechanism of therapeutic action in hypoactive sexual desire disorder.

The hypothetical mechanism of action of flibanserin in HSDD appears to demonstrate a preference for some populations of postsynaptic 5-HT receptors, particularly those that are located on the prefrontal cortex (PFC) pyramidal neurons, which regulate monoamine release in certain selective brain regions.

References

SHOWING 1-10 OF 25 REFERENCES

Receptor reserve for 5-hydroxytryptamine1A-mediated inhibition of serotonin synthesis: possible relationship to anxiolytic properties of 5-hydroxytryptamine1A agonists.

The results suggest that 5- HT1A receptor-mediated regulation of 5-HT synthesis appears to be mediated by somatodendritic autoreceptors on5-HT neurons in the midbrain raphé nuclei, and suggest that these autoreceptor possess a large receptor reserve for agonists.

Central pre- and postsynaptic 5-HT1A receptors in rats treated chronically with a novel antidepressant, cericlamine.

The idea that postsynaptic and somatodendritic 5-HT1A receptors are differently regulated in the rat brain is supported, because only the latter receptors desensitized after a long-term blockade of serotonin reuptake by cericlamine is suggested.

The 5-HT1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo

Findings provide direct neurochemical evidence that by preferentially stimulating somatodendritic 5-HT1A receptors, 8-OH-DPAT inhibits the 5- HT neuronal impulse flow, thereby effectuating decreased terminal 5-hydroxytryptamine synthesis and release.

Modulation of the activity of central serotoninergic neurons by novel serotonin1A receptor agonists and antagonists: a comparison to adrenergic and dopaminergic neurons in rats.

With the exception of (-)-tertatolol, which behaved as a weak agonist, a very similar pattern of inhibition of 5-HT turnover was seen in the striatum, the hippocampus and the hypothalamus (DRN and median raphe nucleus) and the spinal cord, with the Striatum displaying the greatest sensitivity.

Effects of a selective 5‐HT2 agonist, DOI, on 5‐HT neuronal firing in the dorsal raphe nucleus and 5‐HT release and metabolism in the frontal cortex

The results demonstrate that DOI is a potent inhibitor of 5‐HT neuronal firing and terminal release and that the effects on release are not mediated by an action within the terminal region.

The effect of BIMT 17, a new potential antidepressant, in the forced swimming test in mice

Neither the reduction of 5-HT synthesis brought about by p-chlorophenylalanine nor the selective destruction of5-HT containing neurons by 5,7-dihydroxytryptamine reduced the BIMT 17 effect, suggesting that BIMM 17 acts postsynaptically in increasing struggling behaviour.