Flibanserin: First Global Approval

Deeks, Emma D.

doi:10.1007/s40265-015-0474-y

Cited by 25 publications

(28 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For two reasons, subsequent studies evaluated effects of repeated flibanserin doses. First, flibanserin dosing guidelines in humans call for repeated dosing, and full effects of flibanserin on sexual behavior in preclinical studies are also seen primarily following repeated dosing [23]. Second, we have shown previously that repeated drug treatment can unmask expression of abuse-related ICSS rate-increasing effects of some other drugs such as mu opioid receptor agonists [24–27].…”

Section: Introductionmentioning

confidence: 99%

Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats

Lazenka

Blough

Negus

2016

The Journal of Sexual Medicine

View full text Add to dashboard Cite

INTRODUCTION Flibanserin is a serotonin receptor subtype 1A (5HT1A) agonist and 2A (5HT2A) antagonist that has been approved by the Food and Drug Administration for treating female sexual interest/arousal disorder. Little is known about the abuse potential of flibanserin. AIM This study examined abuse-related effects of flibanserin in rats using an intracranial self-stimulation (ICSS) procedure that has been used previously to evaluate abuse potential of other drugs. METHODS Adult female and male Sprague-Dawley rats with electrodes implanted in the medial forebrain bundle were trained to lever press for electrical brain stimulation under a “frequency-rate” ICSS procedure. In this procedure, increasing frequencies of brain stimulation maintain increasing rates of responding. Drugs of abuse typically increase (or “facilitate”) ICSS rates and produce leftward/upward shifts in ICSS frequency-rate curves, whereas drugs that lack abuse potential typically do not alter or only decrease ICSS rates. Initial studies determined the potency and time course of effects on ICSS produced by acute flibanserin (1.0, 3.2 and 10.0 mg/kg). Subsequent studies determined effects of flibanserin (3.2–18 mg/kg) before and after a regimen of repeated flibanserin administration (5.6 mg/kg/day x 5 days). Effects of the abused stimulant amphetamine (1.0 mg/kg) were examined as a positive control. MAIN OUTCOME MEASURE Flibanserin effects on ICSS frequency-rate curves in female and male rats were examined and compared to effects of amphetamine. RESULTS Baseline ICSS frequency-rate curves were similar in female and male rats. Both acute and repeated administration of flibanserin produced only decreases in ICSS rates, and rate-decreasing effects of the highest flibanserin dose (10 mg/kg) were greater in females than males. In contrast to flibanserin, amphetamine produced an abuse-related increase in ICSS rates that did not differ between females and males. CONCLUSIONS These results suggest that flibanserin has low abuse potential. Additionally, this study suggests that females may be more sensitive than males to rate-decreasing effects of high flibanserin doses.

show abstract

Section: Introductionmentioning

confidence: 99%

Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats

Lazenka

Blough

Negus

2016

The Journal of Sexual Medicine

View full text Add to dashboard Cite

show abstract

“…However, literature suggests that flibanserin’s mechanism of action is primarily due to stimulation of 5-HT 1A receptors. [ 33 – 39 ] To investigate the relative contribution of 5-HT 1A versus 5-HT 2A receptor occupancy in flibanserin-mediated neuroprotection, we utilized both a pharmacologic blockade of 5-HT 1A receptors and 5-HT 1A knockout mice. Pharmacologic blockade with 10 mg/kg WAY 100635, a 5-HT 1A antagonist, was administered to BALB/c mice 30 minutes prior to a single dose of 6 mg/kg flibanserin.…”

Section: Resultsmentioning

confidence: 99%

“…Flibanserin, marketed as Addyi ™ (Sprout Pharmaceuticals), was recently approved by the Food and Drug Administration (FDA) for the treatment of hypoactive sexual desire disorder (HSDD). [ 28 – 33 ] Seven phase III clinical trials demonstrated that a daily 100 mg dose of flibanserin was safe and resulted in an improvement of HSDD-related symptoms in pre-menopausal women. [ 30 – 33 ] In CHO cells, flibanserin has a high affinity for serotonergic 5-HT 1A and 5-HT 2A , as well as dopaminergic D 4 receptors, although D 4 receptor binding has yet to be verified in human brain tissue.…”

Section: Introductionmentioning

confidence: 99%

“…[ 28 – 33 ] Seven phase III clinical trials demonstrated that a daily 100 mg dose of flibanserin was safe and resulted in an improvement of HSDD-related symptoms in pre-menopausal women. [ 30 – 33 ] In CHO cells, flibanserin has a high affinity for serotonergic 5-HT 1A and 5-HT 2A , as well as dopaminergic D 4 receptors, although D 4 receptor binding has yet to be verified in human brain tissue. [ 34 – 39 ]…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Retinal Neuroprotective Effects of Flibanserin, an FDA-Approved Dual Serotonin Receptor Agonist-Antagonist

Coyner

Ryals

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

PurposeTo assess the neuroprotective effects of flibanserin (formerly BIMT-17), a dual 5-HT1A agonist and 5-HT2A antagonist, in a light-induced retinopathy model.MethodsAlbino BALB/c mice were injected intraperitoneally with either vehicle or increasing doses of flibanserin ranging from 0.75 to 15 mg/kg flibanserin. To assess 5-HT1A-mediated effects, BALB/c mice were injected with 10 mg/kg WAY 100635, a 5-HT1A antagonist, prior to 6 mg/kg flibanserin and 5-HT1A knockout mice were injected with 6 mg/kg flibanserin. Injections were administered once immediately prior to light exposure or over the course of five days. Light exposure lasted for one hour at an intensity of 10,000 lux. Retinal structure was assessed using spectral domain optical coherence tomography and retinal function was assessed using electroretinography. To investigate the mechanisms of flibanserin-mediated neuroprotection, gene expression, measured by RT-qPCR, was assessed following five days of daily 15 mg/kg flibanserin injections.ResultsA five-day treatment regimen of 3 to 15 mg/kg of flibanserin significantly preserved outer retinal structure and function in a dose-dependent manner. Additionally, a single-day treatment regimen of 6 to 15 mg/kg of flibanserin still provided significant protection. The action of flibanserin was hindered by the 5-HT1A antagonist, WAY 100635, and was not effective in 5-HT1A knockout mice. Creb, c-Jun, c-Fos, Bcl-2, Cast1, Nqo1, Sod1, and Cat were significantly increased in flibanserin-injected mice versus vehicle-injected mice.ConclusionsIntraperitoneal delivery of flibanserin in a light-induced retinopathy mouse model provides retinal neuroprotection. Mechanistic data suggests that this effect is mediated through 5-HT1A receptors and that flibanserin augments the expression of genes capable of reducing mitochondrial dysfunction and oxidative stress. Since flibanserin is already FDA-approved for other indications, the potential to repurpose this drug for treating retinal degenerations merits further investigation.

show abstract

“…Így lehetővé válik, hogy szelektíven csak a tumorsejteket pusztítsuk el, ugyanis a működőképes BRCA1-2-vel rendelkező normál testi sejtek sokkal kevésbé érzékenyek a PARP inhibitorokra [87]. Az Európai Gyógyszer Ügynökség (European Medical Agency, EMA) 2014 decemberében engedélyezte az első PARP inhibitort, az olaparibot (kereskedelmi neve Lynparza), recidiváló, platina-szenzitív serosus petefészek-daganatok harmadik vonalbeli monoterápiájára [88]. A gyógyszer felírási kritériuma a tumor vagy vérmintából igazolt örökletes, vagy szomatikus BRCA1 vagy BRCA2 patogén, illetve nagy valószínűséggel patogén mutáció megléte [89].…”

Section:  Férfi Emlőrák (Bármely éLetkorban)unclassified

A BRCA1 és BRCA2 gének tumorevolúcióban szerepet játszó mutációinak vizsgálata

Enyedi

View full text Add to dashboard Cite

Flibanserin: First Global Approval

Cited by 25 publications

References 23 publications

Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats

Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats

Retinal Neuroprotective Effects of Flibanserin, an FDA-Approved Dual Serotonin Receptor Agonist-Antagonist

A BRCA1 és BRCA2 gének tumorevolúcióban szerepet játszó mutációinak vizsgálata

Contact Info

Product

Resources

About