Flibanserin is a full agonist of the serotonin 5-HT1A receptor and an antagonist of 5-HT2A.
Atypical antipsychotic drugs, all of which are relatively more potent as serotonin (5-HT)(2A) than dopamine D(2) antagonists, improve negative symptoms and cognitive dysfunction in schizophrenia partiallly by increasing cortical dopamine release. 5-HT(1A) agonism is also reported to contribute to the ability to increase cortical dopamine release.
In vitro: Previous study found that flibanserin was a 5-HT(1A) agonist, a very weak partial agonist on dopamine D(4) receptors, and a 5-HT(2A) antagonist. Flibanserin could reduce neuronal firing rate and flibanserin-induced reduction in firing rate was likely mediated via stimulation of postsynaptic 5-HT(1A) receptors. Moreover, flibanserin could quickly desensitize somatic 5-HT autoreceptors and enhance tonic activation of postsynaptic 5-HT(1A) receptors. In addition, flibanserin was able to reduce synthesis and extracellular levels of 5-HT in the cortex [1].
In vivo: Previous animal study showd that flibanserin had antidepressant-like activity in most animal models sensitive to antidepressants, and such activity seemed different from that exerted by other antidepressants. In addition, flibanserin did not show consistent effects in animal models of anxiety and seemed to exert potential antipsychotic effects [1].
Clinical trial: In premenopausal women with HSDD, flibanserin showed significant improvements in the number of SSE and sexual desire. Flibanserin treatment also led to significant reductions in distress associated with sexual dysfunction and distress associated with low sexual desire [2].
References:
[1] Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S. Pharmacology of flibanserin. CNS Drug Rev. 2002 Summer;8(2):117-42.
[2] Katz M et al. Efficacy of flibanserin in women with hypoactive sexual desire disorder: results from the BEGONIA trial. J Sex Med. 2013 Jul;10(7):1807-15.