Pharmacology of flibanserin

Flibanserin has best affection for serotonin 5-HT(1A), dopamine D(4k), and serotonin 5-HT(2A) receptors. In vitro and in microiontophoresis, flibanserin behaves as a 5-HT(1A) agonist, a actual anemic fractional agonist on dopamine D(4) receptors, and a 5-HT(2A) antagonist. In vivo flibanserin binds appropriately to 5-HT(1A) and 5-HT(2A) receptors. However, beneath college levels of academician 5-HT (i.e., beneath stress), flibanserin may absorb 5-HT(2A) receptors in college admeasurement than 5-HT(1A) receptors. The furnishings of flibanserin on adenylyl cyclase are altered from those of buspirone and 8-OH-DPAT, two added declared 5-HT(1A) receptor agonists.

Flibanserin reduces neuronal battlefront amount in beef of the after a rape, hippocampus, and case with the CA1 arena getting the a lot of acute in the brain. Flibanserin-induced abridgment in battlefront amount in the case seems to be advised through dispatch of postsynaptic 5-HT(1A) receptors, admitting the abridgement of the amount of alive beef seems to be advised through dopamine D(4) receptor stimulation. Flibanserin bound desensitizes actual 5-HT autoreceptors in the after raphe and enhances analeptic activation of postsynaptic 5-HT(1A) receptors in the CA3 region. Flibanserin preferentially reduces amalgam and extracellular levels of 5-HT in the cortex, area it enhances extracellular levels of NE and DA.

Flibanserin displays antidepressant-like action in a lot of beastly models acute to antidepressants. Such activity, however, seems qualitatively altered from that exerted by added antidepressants. Flibanserin seems to act via absolute or aberrant dispatch of 5-HT(1A), DA, and opioid receptors in those beastly models. Flibanserin does not affectation constant furnishings in beastly models of all-overs and seems to apply abeyant antipsychotic effects. Flibanserin may abet some balance but does not abet appreciable baneful furnishings at pharmacologically accordant doses.

Flibanserin acts as a full agonist in the frontal cortex and the raphe dorsalis, but only as a partial agonist in the CA3 region of the hippocampus of the 5-HT1A receptor (Ki = 1 nM in CHO cells, but only 15–50 nM in cortex, hippocampus and dorsal raphe) and, with lower affinity, as an antagonist of the 5-HT2A receptor (Ki = 49 nM) and antagonist or very weak partial agonist of the D 4 receptor (K i = 4–24 nM).