Effects of a new type of 5-HT receptor agonist on male rat sexual behavior

Ahlénius, Sven; Larsson, Knut; Svensson, Lennart; Stephan, Holger; Carlsson, Arvid; Lindberg, Per; Wikström, Håkan; Sánchez, Domènec J.; Arvidsson, L.-E.; Hacksell, Uli; Nilsson, Jonas

doi:10.1016/0091-3057(81)90023-x

Cited by 312 publications

(146 citation statements)

References 31 publications

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“…This ejaculatory reflex has been shown to be controlled primarily by both serotonin and dopamine (McMahon, 2004). Among the different subtypes of 5-HT receptors, the most important ones on ejaculation are 5-HT 1A , 5-HT 1B , and 5-HT 2C receptors (Ahlenius et al, 1981). Because the rapid onset of postponement of ejaculation by some of the SSRIs has a similar time course as their synaptic effect on 5-HT, it is suggested that the effect on ejaculation is mediated by acute enhancement of 5-HT neurotransmission or by differential activation of different 5-HT receptor populations, notably 5-HT 1A and 5-HT 2C receptors (Szele et al, 1988;Molewijk et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Safety and Efficacy of Dapoxetine in the Treatment of Premature Ejaculation: A Double-Blind, Placebo-Controlled, Fixed-Dose, Randomized Study

Safarinejad¹

2007

Neuropsychopharmacol

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The aim of the study was to evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) drug dapoxetine in delaying ejaculation in patients with premature ejaculation (PE). A total of 212 potent men with PE were randomly assigned to receive 30 mg orally dapoxetine (group 1, N ¼ 106) twice daily or similar regimen of placebo (group 2, N ¼ 106) during a 12-week period for each agent. Pretreatment evaluation included history and physical examination, geometric mean intravaginal ejaculatory latency time (IELT, primary outcome measure), and International Index of Erectile Function (IIEF). The efficacy of two treatments was assessed every 2 weeks during treatment, at the end of study, and in 3-month follow-up after cessation of treatment. We measured geometric mean IELT. Thus, the IELT values were logarithmically transformed before statistical analysis, and the results are reported as fold increases from baseline with associated 95% confidence intervals (CI). The independent sample two-tailed t-test was used to compare the IELTs. At the end of 12-week treatment, the dapoxetine group had a 2.9-(95% CI, 1.84-4.16) fold increase of the geometric mean IELT, while after placebo the geometric mean IELT did not increase significantly (1.4-fold increase; 95% CI, 0.84-1.63) (p ¼ 0.001). The mean weekly intercourse episodes increased from pretreatment values of 1.16 and 1.14 to 2.2 and 1.4, for dapoxetine and placebo, respectively (p ¼ 0.04). Baseline mean intercourse satisfaction domain values of IIEF, 12 and 11, reached to 16 and 10 at the 12-week treatment in groups 1 and 2, respectively (p ¼ 0.04). At the end of 3-month follow-up period, the geometric mean IELT in dapoxetine and placebo group demonstrated 1.4-(95% CI, 0.66-1.46) and 1.3-(95% CI, 0.77-1.63) fold increase, respectively (p ¼ 0.1). Three-month intercourse satisfaction domain value of IIEF was 11 in group 1 and 10 in group 2 (p ¼ 0.1). Mean number of adverse events was 19 for dapoxetine and 7 for placebo (p ¼ 0.02). Dapoxetine has moderately better results in terms of IELT and intercourse satisfaction vs placebo without long-term benefit for the patient after it is withdrawn. Further studies are necessary to draw final conclusions on the efficacy of this drug in PE.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Safety and Efficacy of Dapoxetine in the Treatment of Premature Ejaculation: A Double-Blind, Placebo-Controlled, Fixed-Dose, Randomized Study

Safarinejad¹

2007

Neuropsychopharmacol

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“…In the central 5-HT pathways the 5-HT 1A receptors decrease erection and latency to ejaculation in male rats, 19,20 whereas the 5-HT 2C receptors increase both erection and latency of ejaculation. 20,21 Studies investigating the relationship between 5-HT and sexual hormones have shown that oestradiol was reported to induce a desensitization of the 5-HT 1A receptors. 22,23 Both estrone and oestradiol are increased in obese men compared with control subjects, a finding attributed to increased peripheral aromatization of androgens.…”

Section: Discussionmentioning

confidence: 99%

Insight on pathogenesis of lifelong premature ejaculation: inverse relationship between lifelong premature ejaculation and obesity

Gökçe

Ekmekçioğlu

2010

Int J Impot Res

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Although both biological and psychological factors are important in the etiology, the exact pathogenesis of lifelong premature ejaculation (PE) remains to be clarified. Obesity is a worldwide epidemic that contributes to many chronic diseases. Obesity is associated with erectile dysfunction, but the relationship between obesity and PE has not yet been specifically investigated. The aim of this study was to evaluate the relationships of these two conditions. Between January 2008 and December 2009, we evaluated consecutive patients with lifelong PE in the urology outpatient clinic. Control cases without lifelong PE were selected randomly among cases attending the department of internal medicine for a checkup procedure. The age and sex of control group were matched with that of the study group. Body mass index (BMI) of each case was calculated using the World Health Organization criteria by the measurements of the physician instead of relying on verbal expressions. The mean (±s.d.) age of the premature ejaculators was 31.7±5.7 (range 21-51) years and in the control cases it was 32.3±6.7 (range 22-54) years. The comparison of the mean (±s.d.) weight between the study (74.1 ± 11.2 kg) and control groups (81.9 ± 6.4 kg) revealed a significant difference (Po0.001). The mean BMI of premature ejaculators (24.9 ± 3.4 kg m -2 ) was lower than the mean BMI of control (27.5±3.6 kg m -2 ; Po0.001). As the BMI increased, the number of patients decreased in the PE group. The number of the obese cases in the control group (n ¼ 26, 24.1%) was three times greater than the obese premature ejaculators (Po0.005), and the number of PE patients were approximately two times greater than the control cases in the normal-weight class (Po0.001). This is the first prospective study that investigated the relationship between lifelong PE and obesity, and we found that patients with lifelong PE were leaner than the healthy control cases.

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“…One of the receptors involved is the 5-HT 1A receptor, located as a somatodendritic autoreceptor on 5-HT cell bodies and as postsynaptic heteroreceptor on many nonserotonergic neurons in various brain areas [42]. 5-HT 1A receptor agonists including buspirone have prosexual activity in rats upon acute administration [43,44]. Extensive evidence suggests that this prosexual activity of 5-HT 1A R agonists is most likely due to activation of postsynaptic 5-HT 1A receptors that probably mediate dopaminergic activation in brain areas that decrease the ejaculation threshold [44].…”

Section: Sexual Dysfunctionmentioning

confidence: 99%

Sexual Dysfunction, Depression and Antidepressants: A Translational Approach

Olivier¹,

Franco²,

Waldinger³

et al. 2017

Sexual Dysfunction

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Major depression is frequently associated with sexual dysfunctions. Most antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), induce additional sexual side effects and, although effective antidepressants, deteriorate sexual symptoms, which are the main reason that patients stop antidepressant treatment. Many strategies have been used to circumvent the additional sexual side effects, but results are rather disappointing. Recently, new antidepressants have been introduced, vilazodone and vortioxetine, which seem to lack sexual side effects in the early registration trials. Much research with large numbers of depressed patients and adequate methodological tools still has to confirm in daily use the absence of sexual side effects of new antidepressants. Animal models that in an early phase of drug development may predict putative sexual side effects of new antidepressants are extremely useful and could speed up development of new antidepressants. A rat model of sexual behavior is described that has a very high predictive validity for sexual side effects in man. Several characteristics of present antidepressants with regard to sexual dysfunctions are also present in the rat model and establish its validity. The animal model can also be used in the search for new psychotropics without sexual side effects or for drugs with sexual stimulating activity.

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Effects of a new type of 5-HT receptor agonist on male rat sexual behavior

Cited by 312 publications

References 31 publications

RETRACTED ARTICLE: Safety and Efficacy of Dapoxetine in the Treatment of Premature Ejaculation: A Double-Blind, Placebo-Controlled, Fixed-Dose, Randomized Study

RETRACTED ARTICLE: Safety and Efficacy of Dapoxetine in the Treatment of Premature Ejaculation: A Double-Blind, Placebo-Controlled, Fixed-Dose, Randomized Study

Insight on pathogenesis of lifelong premature ejaculation: inverse relationship between lifelong premature ejaculation and obesity

Sexual Dysfunction, Depression and Antidepressants: A Translational Approach

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