Mechanism of action
Activity profile
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 (serotonin 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 D4 receptor (Ki = 4–24 nM). Despite the much greater affinity of flibanserin for the 5-HT1A receptor, and for reasons that are unknown (although it might be caused by the competition with endogenous serotonin), flibanserin occupies the 5-HT1A and 5-HT2A receptors in vivo with similar percentages. Flibanserin also has low affinity for the 5-HT2B receptor (Ki = 89.3 nM) and the 5-HT2C receptor (Ki = 88.3 nM), both of which it behaves as an antagonist of. Flibanserin preferentially activates 5-HT1A receptors in the prefrontal cortex, demonstrating regional selectivity, and has been found to increase dopamine and norepinephrine levels and decrease serotonin levels in the rat prefrontal cortex, actions that were determined to be mediated by activation of the 5-HT1A receptor. As such, flibanserin has been described as a norepinephrine–dopamine disinhibitor (NDDI).The proposed mechanism of action refers to the Kinsey dual control model of sexual response. Various neurotransmitters, sex steroids, and other hormones have important excitatory or inhibitory effects on the sexual response. Among neurotransmitters, excitatory activity is driven by dopamine and norepinephrine, while inhibitory activity is driven by serotonin.
Pelvic organ prolapse (POP) is characterized by descent of pelvic organs from their normal positions. In women, the condition usually occurs when the pelvic floor collapses after gynecological cancer treatment, childbirth or heavy lifting.In men, it may occur after the prostate gland is removed. The injury occurs to fascia membranes and other connective structures that can result in cystocele, rectocele or both. Treatment can involve dietary and lifestyle changes, physical therapy, or surgery. Types
Anterior vaginal wall prolapse
Cystocele (bladder into vagina)
Urethrocele (urethra into vagina)
Cystourethrocele (both bladder and urethra)
Posterior vaginal wall prolapse
Enterocele (small intestine into vagina)
Rectocele (rectum into vagina)
Sigmoidocele
Apical vaginal prolapse
Uterine prolapse (uterus into vagina)
Vaginal vault prolapse (roof of vagina) – after hysterectomy

Grading
Pelvic organ prolapses are graded either via the Baden–Walker System, Shaws System, or the Pelvic Organ Prolapse Quantification (POP-Q) System. Shaws System
Anterior wall

Upper 2/3 cystocele
Lower 1/3 urethrocelePosterior wall

Upper 1/3 enterocele
Middle 1/3 rectocele
Lower 1/3 deficient perineumUterine prolapse

Grade 0 Normal position
Grade 1 descent into vagina not reaching introitus
Grade 2 descent up to the introitus
Grade 3 descent outside the introitus
Grade 4 Procidentia

Baden–Walker
POP-Q
Management
Vaginal prolapses are treated according to the severity of symptoms. Non-surgical
With conservative measures, such as changes in diet and fitness, Kegel exercises, and pelvic floor physical therapy.With a pessary, a rubber or silicone rubber device fitted to the patient which is inserted into the vagina and may be retained for up to several months. Pessaries are a good choice of treatment for women who wish to maintain fertility, are poor surgical candidates, or who may not be able to attend physical therapy.