Pharmacology of serotonin and female sexual behavior

Uphouse, Lynda

doi:10.1016/j.pbb.2013.11.008

Cited by 38 publications

(34 citation statements)

References 199 publications

(286 reference statements)

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“…Differential roles of different 5-HT receptor activation on sexual behavior may explain some of these inconsistencies (25). Most evidence indicates that 5-HT 1 A receptor agonists inhibit sexual behavior, while 5-HT 2 or 5-HT 3 receptors may exert a positive influence (26). One of the assumed hypotheses for SSRI-induced loss of sexual desire is the role of the 5-HT1A receptor-mediated norepinephrine neurotransmission.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of cognitive behavioral therapy and fluoxetine on sexual function of women with obsessive compulsive disorder: A double-blind randomized controlled trial

Sabetnejad¹,

Assarian²,

Omidi³

et al. 2016

Electron physician

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BackgroundObsessive compulsive disorder (OCD) is a mental health concern due to its various negative consequences, especially in sexual function. Therefore, the treatment of sexual dysfunction in women with OCD is important in order to improve the patient’s marital function and mental health.ObjectivesTo compare the sexual behavior and sexual and marital satisfaction in women with obsessive-compulsive disorder (OCD) before and after treatment with fluoxetine and cognitive behavior therapyMethodsThis randomized clinical trial was conducted at psychiatric and psychological counseling centers in Kashan (Iran) from January 2, 2014, to December 29, 2014. Fifty-eight women with OCD were included in the study. In order to compare the effectiveness of pharmacological treatment (fluoxetine) and psychological treatment, cognitive behavior therapy (CBT), 58 female patients with OCD (diagnosed based on DSM-IV-T criteria) were randomized equally to either fluoxetine (at a dose of 60–80 mg daily for 3 months) or CBT (10 45-minute sessions). OCD and sexual behavior status of the patients before and after the intervention was assessed with the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) and Female Sexual Function Index (FSFI) questionnaire, respectively. The data were analyzed using SPSS version 22. To compare changes between the two groups, an independent T-test was used. Finally, the effects of all potential factors on treatment outcome were analyzed using factorial ANCOVA.ResultsThe mean score for OCD in the fluoxetine group was 25.6 ± 4.8 at the beginning of the experiment and 18.79 ± 4.26 at the end of the study, while in the CBT group it was 25.6 ± 4.8 and 18.79 ± 4.26, respectively. No significant differences were found between two groups regarding obsession score changes. These scores in fluoxetine group were 58.1 and 52.8, respectively (p=0.046). There was a significant difference between the two groups in terms of sexual performance (p=0.003).ConclusionIn this study, our findings demonstrate a significant reduction in symptom severity of OCD after treatment with fluoxetine and CBT, indicating CBT can be an alternative for fluoxetine therapy in such patients. Therefore, both pharmacotherapy and CBT can be used for this purpose in clinical practices, but more studies are needed.Clinical trial registrationThe trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT2013091014619N1.FundingThe authors received no financial support for the research, authorship, and/or publication of this article.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of cognitive behavioral therapy and fluoxetine on sexual function of women with obsessive compulsive disorder: A double-blind randomized controlled trial

Sabetnejad¹,

Assarian²,

Omidi³

et al. 2016

Electron physician

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“…An example of renewed interest in a previous GPCR target that had resulted in an approved drug that was later withdrawn is that of the cannabinoid receptors, which are now being explored for neuroprotection, inflammation and osteoporosis [52]. GPCR drugs for improvement of quality of life are also under development, such as mixed serotonin receptor 5HT 1A agonist and 5HT 2A antagonist flibanserin 26 for treatment of female hypoactive sexual desire disorder [53]. Newly revealed biological actions of previously underexplored GPCRs, such as the hundreds of olfactory receptors [106,145] and a 33-membered family of adhesion GPCRs [54], are providing new avenues for translational development.…”

Section: New Pharmacological Dimensionsmentioning

confidence: 99%

New paradigms in GPCR drug discovery

Jacobson

2015

Biochemical Pharmacology

153

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G protein-coupled receptors (GPCRs) remain a major domain of pharmaceutical discovery. The discovery of GPCR lead compounds and their optimization are now structure-based, thanks to advances in X-ray crystallography, molecular modeling, protein engineering and biophysical techniques. In silico screening provides useful hit molecules. New pharmacological approaches to tuning the pleotropic action of GPCRs include: allosteric modulators, biased ligands, GPCR heterodimer-targeted compounds, manipulation of polypharmacology, receptor antibodies and tailoring of drug molecules to fit GPCR pharmacogenomics. Measurements of kinetics and drug efficacy are factors influencing clinical success. With the exception of inhibitors of GPCR kinases, targeting of intracellular GPCR signaling or receptor cycling for therapeutic purposes remains a futuristic concept. New assay approaches are more efficient and multidimensional: cell-based, label-free, fluorescence-based assays, and biosensors. Tailoring GPCR drugs to a patient’s genetic background is now being considered. Chemoinformatic tools can predict ADME-tox properties. New imaging technology visualizes drug action in vivo. Thus, there is reason to be optimistic that new technology for GPCR ligand discovery will help improve the current narrowing of the pharmaceutical pipeline.

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“…Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are associated with the greatest prevalence of sexual dysfunction in humans (Montgomery et al 2002; Outhoff 2010) and have been the most investigated in animal models (Uphouse 2014). However, in a majority of such studies, only the consummatory response (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…This is unfortunate given the predominant complaints regarding sexual desire/arousal in humans, which may be better regarded as decrements in appetitive and precopulatory systems. Although animal models of female sexual motivation have been developed that are effective in differentiating hormonally-primed from nonhormonally-primed ovariectomized rats (Clark et al 2004; Erskine 1989; Pfaus et al 1999), such models have been surprisingly insensitive to the effects of antidepressants such as SSRIs (Sarkar et al 2008; Uphouse 2014). …”

Section: Introductionmentioning

confidence: 99%

Use of an operant paradigm for the study of antidepressant-induced sexual dysfunction

Uphouse

Pinkston

Baade

et al. 2015

Behavioural Pharmacology

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These studies were designed to develop a paradigm for detection of antidepressant-induced sexual dysfunction in female rats. Ovariectomized, Fischer rats were conditioned to nose poke to open a guillotine door to gain access to a sexually active male. To develop the procedure, we examined the acquisition and stability of the response with a 15 s fixed interval, compared rats treated with 10 μg estradiol benzoate and 500 μg progesterone to those that received only estradiol benzoate, and performed a preliminary analysis of effects of 5, 10 and 15 mg/kg fluoxetine. We then more fully evaluated the effects of 5 mg/kg fluoxetine. Fluoxetine reduced sexual motivation as assessed by the number of nose pokes, number of nose poke episodes, and by the latency to approach the male. In addition, changes in the female’s sexual motivation were examined before and after ejaculation during the final conditioning trials. The number of nose pokes was reduced and the latency to initiate a new nose poke episode was increased following ejaculation. The robustness of the antidepressant-induced decline in sexual motivation is in marked contrast to findings with several other animal models for sexual dysfunction and illustrates the usefulness of the operant procedure.

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Pharmacology of serotonin and female sexual behavior

Cited by 38 publications

References 199 publications

Effectiveness of cognitive behavioral therapy and fluoxetine on sexual function of women with obsessive compulsive disorder: A double-blind randomized controlled trial

Effectiveness of cognitive behavioral therapy and fluoxetine on sexual function of women with obsessive compulsive disorder: A double-blind randomized controlled trial

New paradigms in GPCR drug discovery

Use of an operant paradigm for the study of antidepressant-induced sexual dysfunction

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