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François Giuliano

Publications and source records attributed to François Giuliano.

At least 19 recordsLinked to original sources
PubMed2006

5-Hydroxytryptamine in premature ejaculation: opportunities for therapeutic intervention.

Ejaculation, although mediated by a spinal ejaculation generator, is subject to descending supraspinal modulation from several brain regions. 5-Hydroxytryptamine (5-HT or serotonin) is involved in ejaculatory control, with its ejaculation-retarding effects likely to be attributable to activation of 5-HT1B and 5-HT2C receptors, both spinally and supraspinally. By contrast, stimulation of 5-HT1A receptors precipitates ejaculation. Selective serotonin reuptake inhibitors (SSRIs), which are used for treatment of psychiatric disorders, can delay ejaculation in humans and are widely used 'off-label' for treatment of premature ejaculation. SSRIs require 1-2 weeks' chronic dosing to be effective, similar to their use for treatment of depression. However, a new short-acting SSRI is effective 'on demand' and might represent the first of a new generation of therapies targeted to premature ejaculation.

Animals↗
PubMed2006

The melanocortin agonist, melanotan II, enhances proceptive sexual behaviors in the female rat.

Melanocortins have been reported to play a role in the control of both male and female sexual behavior. The present study examined the effects of melanotan-II (MT-II), a cyclic peptide analogue of alpha-melanocyte stimulating hormone on appetitive and consummatory aspects of female sexual behavior, including aspects of sexual proceptivity (solicitations, hops and darts, ear wiggling, pacing) and receptivity (lordosis). One group of ovariectomized Long-Evans rats (n=7) was primed subcutaneously with estradiol benzoate (EB) and progesterone (P) (10 microg and 500 microg respectively) and another group (n=7) with EB (10 microg) and oil (EB alone). Paced mating tests were performed with sexually experienced males in unilevel chambers, which were bisected by a Plexiglas divider containing three holes, through which only the female could pass. MT-II (1 and 3 mg/kg) or saline was injected intravenously 10 min before each 30-min paced mating test. Each female received the 3 treatments. In females primed with EB+P both doses of MT-II increased the number of hops and darts and ear wiggling significantly, but did not alter pacing or lordosis. With EB alone, no effect of MT-II was observed on any of the parameters measured. These results suggest that P can interact with MT-II to increase proceptive behaviors. Because hops and darts are essentially solicitations, made in close proximity to the male, that indicate a desire on the part of females to receive mounts and intromissions, these data suggest that activation of melanocortin receptors may represent a promising mode of action for the treatment of women with hypoactive sexual desire.

Animals↗
PubMed2006

Relaxation of phasic contractile activity of human detrusor strips by cyclic nucleotide phosphodiesterase type 4 inhibition.

OBJECTIVES: Detrusor smooth muscle relaxation is mainly mediated by the cyclic adenosine monophosphate (cAMP) pathway. Elevation of cAMP levels by phosphodiesterase type 4 (PDE4) inhibition relaxes smooth muscles of various origins. We aimed to determine the effect of a PDE4 inhibitor, rolipram, on human detrusor contractions. METHODS: Human bladder strips (from 20 different donors) with no known overactive bladder (OAB) were studied in organ baths. Detrusor samples with or without urothelium were incubated with carbachol 10(-6)mol/l (in presence or absence of forskolin, 3.10(-7)mol/l) or with KCl 10mmol/l to enhance phasic contractile activity. Concentration response curves for rolipram or vehicle were then performed. RESULTS: Rolipram (10(-9) to 3.10(-5)mol/l) induced a moderate relaxing effect on carbachol-induced contractions. This effect was enhanced when cAMP levels were increased by forskolin (the maximal effect was 53.0+/-5.1 vs. 83.1+/-5.7%, p<0.01) or in strips with urothelium. In contrast, rolipram (10(-9) to 10(-4)mol/l) drastically inhibited phasic contractile activity: The developed tension, the area under the curve, and the amplitude of phasic activity were reduced to 64.8+/-3.6, 91.2+/-5.3, and 82.3+/-7.3%, respectively, versus 23.6+/-9.5, 34.7+/-18.8, and 18.0+/-16.2% for vehicle, respectively (p<0.05). Frequency of phasic activity was 0.96+/-0.45 contractions per minute versus 2.6+/-0.18 for vehicle (p<0.001). In strips with urothelium, the inhibitory effect of rolipram on phasic contractile activity was similar. CONCLUSIONS: PDE4 isoenzymes are strongly involved in the regulation of phasic myogenic activity of human bladder strips. Because an increase of this phasic activity may play a role in the pathophysiology of detrusor overactivity, PDE4 inhibitors might represent an attractive strategy for the treatment of OAB.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine.

OBJECTIVES: The aim of the study was to determine whether dapoxetine, a short-acting selective serotonin reuptake inhibitor, acts at the spinal or supraspinal level to inhibit the ejaculatory reflex. METHODS: The pudendal motoneuron reflex discharges (PMRDs) model was used as an experimental paradigm of the ejaculatory expulsion reflex in anaesthetised male rats. A spinal site of action was evaluated by testing the effect of intrathecal delivery of dapoxetine on PMRDs elicited by electric stimulation of the dorsal nerves of the penis (DNP). A supraspinal site of action was evaluated by testing the effect of intravenous administration of dapoxetine on DNP-induced PMRDs in rats with chemical bilateral lesion of the lateral paragigantocellular nucleus (LPGi). RESULTS: Compared with control (NaCl 0.9%, intrathecally), intrathecal injection of dapoxetine (1 and 80 microg) significantly increased amplitude of DNP-elicited PMRDs in a similar fashion than serotonin (5-HT; 10 and 100 microg, intrathecally). In rats having received bilaterally NaCl 0.9% into LPGi, intravenous treatment with dapoxetine (3mg/kg) induced significant delay in PMRD latency and decrease in PMRD amplitude compared with pretreatment values. These effects were abolished in rats having received bilaterally kainic acid into LPGi 1 d before testing. CONCLUSIONS: The present study showed that dapoxetine inhibits ejaculatory expulsion reflex by acting at a supraspinal level with LPGi as a necessary brain structure for this effect.

Animals↗
PubMed2006

Serotonin and premature ejaculation: from physiology to patient management.

INTRODUCTION: Premature ejaculation (PE), whose pathophysiology is still not clearly identified, is the most common male sexual dysfunction, yet it remains underdiagnosed and undertreated. The aims of this paper are to provide a scientific and pharmacologic rationale, and to discuss to what extent selective serotonin reuptake inhibitors (SSRIs) can help patients with PE. MATERIALS AND METHODS: A comprehensive evaluation of available published data included analysis of published full-length papers that were identified with Medline and Cancerlit from January 1981 to January 2006. Official proceedings of internationally known scientific societies held in the same time period were also assessed. RESULTS: The central ejaculatory neural circuit comprises spinal and cerebral areas that form a highly interconnected network. The sympathetic, parasympathetic, and somatic spinal centers, under the influence of sensory genital and cerebral stimuli integrated and processed at the spinal cord level, act in synergy to command physiologic events occurring during ejaculation. Experimental evidence indicates that serotonin (5-HT), throughout brain descending pathways, exerts an inhibitory role on ejaculation. To date, three 5-HT receptor subtypes (5-HT1A, 5-HT1B, and 5-HT2C) have been postulated to mediate 5-HT's modulating activity on ejaculation. Pharmacologic manipulation of the serotonergic system has been performed in rats, with the antidepressant selective serotonin reuptake inhibitors (SSRIs) exhibiting the greatest efficacy in delaying ejaculation. The mechanism of action by which SSRIs modulate central 5-HT tone has been studied in depth, but gaps in this knowledge prevent an explanation of the efficacy of acute treatment in delaying ejaculation. Emerging clinical evidence indicates chronic and on-demand dosing of SSRIs has a beneficial effect for the treatment of men with PE, at least for paroxetine. On-demand dapoxetine, and SSRI with a short half-life, recently has been shown to significantly increase intravaginal latency time and PE patient-related outcomes in phase 3 clinical trials. CONCLUSIONS: Nowadays there is no doubt that PE can be treated effectively by SSRIs. Nevertheless their mechanism of action is not yet well understood and deserves more research. In particular it is not understood why all the SSRIs are not equal in terms of their ability to delay ejaculation. Therefore, there is a need for more research to better characterize the mechanism of action of SSRIs as well their clinical benefit in patients affected by PE.

Animals↗
PubMed2006

Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5mg and 10mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Erectile dysfunction (ED) is a chronic disease; however, therapy is currently administered as needed with oral phosphodiesterase 5 (PDE5) inhibitors like tadalafil. Because the 17.5-h half-life of tadalafil enables therapeutic plasma levels to be sustained with daily administration, tadalafil is a good candidate for once daily dosing therapy. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, 12-week study enrolled 268 men 1:2:2 to placebo, tadalafil 5mg, and tadalafil 10mg taken once daily. Primary efficacy measures included changes in the International Index of Erectile Function Erectile Function domain (IIEF EF), Sexual Encounter Profile diary Questions 2 (SEP2: successful penetration), and 3 (SEP3: successful completion of intercourse), and tolerability. Secondary measures included percentage of patients at endpoint who reported improved erectile function (EF), and percentage who reported "no ED" (IIEF EF score 26-30). RESULTS: For patients who took placebo, tadalafil 5mg, and tadalafil 10mg, changes from baseline to endpoint were, respectively, 0.9, 9.7, and 9.4 for IIEF EF; 11.2, 36.5, and 39.4 for SEP2; and 13.2, 45.5, and 50.1 for SEP3. At endpoint, 28.3%, 84.5%, and 84.6% reported improved erections, and 8.3%, 51.5%, and 50.5% reported "no ED," respectively. All comparisons between tadalafil and placebo were significant (p<0.001). Adverse events that occurred in at least 5% of patients were dyspepsia, headache, back pain, upper abdominal pain, and myalgia; nine patients (3.4%) discontinued because of adverse events. CONCLUSIONS: Once-a-day tadalafil 5mg or 10mg was well tolerated and significantly improved EF in men with ED.

Adult↗
PubMed2006

Role of peripheral innervation in p-chloroamphetamine-induced ejaculation in anesthetized rats.

The occurrence of ejaculation, which consists of 2 distinct phases (emission and expulsion), requires a tight coordination of peripheral autonomic and somatic nerves. However, some aspects of the mechanism of ejaculation are not clearly defined. To clarify this issue, we used the p-chloroamphetamine (PCA)-induced ejaculation model in anesthetized rats and investigated the effects of selective peripheral nerves lesions on seminal vesicle and bulbospongiosus (BS) muscle activities as representing physiological markers of emission and expulsion phases, respectively. In intact rats, ejaculation induced with PCA (intraperitoneal 5 mg/kg) correlated with coordinated increases in seminal vesicle pressure (SVP) and BS electromyographic activity. PCA-induced ejaculation was still observed in rats with bilateral lesion of hypogastric nerves (HNx), lumbar paravertebral sympathetic chain (LSCx), or dorsal nerves of the penis (DNPx). Conversely, bilateral section of pelvic nerves (PNx) or L6-S1 dorsal roots (DRx) abolished PCA-induced ejaculation. The amplitude of SVP increases induced by PCA was reduced in PNx, HNx, and LSCx rats, whereas it was unchanged in DRx and DNPx rats. The time interval between SVP increases and BS muscle contractions induced by PCA was comparable in the different neural lesion groups. In conclusion, PCA initiates both emission and expulsion independently from each other. In this model, afferents conveyed by the pelvic nerves appear to be unnecessary for occurrence of BS muscle contractions but are essential for a complete ejaculatory response.

Animals↗
PubMed2006

Hemodynamic interaction study between the alpha1-blocker alfuzosin and the phosphodiesterase-5 inhibitor tadalafil in middle-aged healthy male subjects.

OBJECTIVES: To examine the hemodynamic interactions of the phosphodiesterase type 5 (PDE-5) inhibitor tadalafil with the uroselective alpha1-blocker alfuzosin (10 mg daily), commonly prescribed for benign prostatic hyperplasia-related lower urinary tract symptoms. Erectile dysfunction is commonly associated with lower urinary tract symptoms. PDE-5 inhibitors are the first-line treatment of choice for erectile dysfunction. When co-administered with alpha1-blockers, PDE-5 inhibitors could induce orthostatic hypotension. METHODS: During each of the two periods of a randomized, double-blind, placebo-controlled, crossover study, 18 healthy middle-aged men received alfuzosin 10 mg daily for 7 days and either a single 20-mg dose of tadalafil or placebo on day 7. The blood pressure and heart rate were monitored before and for 24 hours after tadalafil or placebo. RESULTS: The combination of tadalafil 20 mg with alfuzosin 10 mg daily elicited a maximal decrease in standing systolic blood pressure that was not significantly different from that after placebo (mean difference 4.35 mm Hg, P = nonsignificant). Analysis of the blood pressure outliers showed that only 1 subject had an asymptomatic standing systolic blood pressure of less than 85 mm Hg. No vasodilatory adverse events were observed with the combined medication. CONCLUSIONS: In healthy, middle-aged men, tadalafil 20 mg showed no clinically relevant hemodynamic interactions with alfuzosin 10 mg daily.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Effects of potassium channel modulators on human detrusor smooth muscle myogenic phasic contractile activity: potential therapeutic targets for overactive bladder.

OBJECTIVES: Increased urinary bladder detrusor smooth muscle phasic contractility has been suggested to be associated with idiopathic bladder overactivity (OAB). We examined the role of voltage-dependent L-type calcium channels, adenosine triphosphate-sensitive potassium (K(ATP)) channels, and calcium-activated potassium (BK(Ca) and SK(Ca)) channels in the regulation of human detrusor phasic contractile activity. METHODS: Isolated human bladder strip phasic contractions were measured and quantified as the mean area under the force-time curve, amplitude, and frequency of phasic contractions in 22 bladder samples. RESULTS: Human detrusor strips displayed myogenic phasic contractions in the presence of atropine (10(-6) M), phentolamine (10(-6) M), propranolol (10(-6) M), suramin (10(-5) M), and tetrodotoxin (10(-6) M). The L-type calcium channel inhibitor nifedipine (300 nM) abolished the contractile activity. Blockade of K(ATP) channels by glibenclamide (1 and 10 microM) did not alter myogenic contractions. In contrast, the K(ATP) channel opener pinacidil (10 microM) markedly inhibited phasic contractility. Iberiotoxin (100 nM) and apamin (100 nM), potent and selective inhibitors of BK(Ca) and SK(Ca) channels, respectively, significantly increased the area under the force-time curve and the amplitude of contractions. CONCLUSIONS: Phasic contractions of human detrusor are dependent on calcium entry through L-type calcium channels. BK(Ca) and SK(Ca) channels play a key role in the modulation of human detrusor smooth muscle phasic contractility. Furthermore, these observations support the concept that increasing conductance through K(ATP), BK(Ca), and SK(Ca) channels may represent attractive pharmacologic targets for decreasing phasic contractions of detrusor smooth muscle in OAB.

Calcium Channels, L-Type↗
PubMed2006

Research instruments for the diagnosis and treatment of patients with erectile dysfunction.

As the incidence and prevalence of erectile dysfunction (ED) increase, healthcare providers will require robust, accurate, and efficient tools for appropriately diagnosing and treating patients with ED. Moreover, clinicians will need effective follow-up tools that assess treatment efficacy and satisfaction, to help patients meet their expectations for successful treatment of ED. We provide a summary of some of the most commonly used instruments for the diagnosis and assessment of ED treatment efficacy that will be referred to in this supplement.

Diagnostic Techniques, Urological↗
PubMed2006

How, why and when should urologists evaluate male sexual function?

Male sexual dysfunction-a term that is commonly used to refer to erectile dysfunction, premature ejaculation, decreased libido and impaired orgasm-is the primary complaint encountered by many urologists. Despite the high prevalence and bothersome nature of these complaints, they are frequently neglected in clinical practice. This paper highlights clinical situations in which urologists should systematically evaluate male sexual functioning. These include men who present with several common urologic disorders, such as pelvic trauma, malignancies, and lower urinary tract symptoms associated with benign prostatic hyperplasia, neurologic disorders and infertility. Studies have shown that erectile dysfunction might be a clinical marker of endothelial dysfunction, and consequently of undetected diabetes, hypertension, dyslipidemia, coronary artery disease and depression. We also address the question of whether urologists should adopt wide-ranging screening regimens for sexual dysfunction.

Humans↗
PubMed2006

Effect of the 5-HT receptor agonist DOI on female rat sexual behavior.

INTRODUCTION: Female rats display a repertoire of behaviors during a sexual encounter with a male, including sexually receptive (the lordosis response) and proceptive (darts and hops, and ear wigglings) behaviors. AIM: We investigated the effects of subcutaneous injection of the 5-HT(2A/2C) receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) on sexual behaviors of ovariectomized female rat hormonally supplemented with estradiol benzoate (10 microg) and progesterone (250 microg). METHODS: Both female and male sexual behaviors were observed for 10 minutes (pretest). Then females were injected with the treatment and after a 10-minute delay replaced with the same male for a 30-minute mating test (posttreatment period). RESULTS: DOI (0.5 and 1 mg/kg) significantly increased the number of darts and hops/mounts. In contrast, no significant differences in ear wigglings/mounts were observed. In addition, DOI failed to modify sexual receptivity. CONCLUSION: These data suggest that 5-HT(2A/2C) receptors are important in the regulation of female proceptivity.

Amphetamines↗
PubMed2006

Erectile dysfunction in hypercholesterolemic atherosclerotic apolipoprotein E knockout mice.

INTRODUCTION: Erectile dysfunction (ED) and cardiovascular diseases share the same risk factors. Although the use of hypercholesterolemic rabbit models has proven to be useful to illustrate the link between ED and hypercholesterolemia, the cost of daily maintenance of the animals and necessity for important amounts of drug have limited their use. AIM: We aimed to develop a new model of atherosclerosis-associated ED in a well-known experimental model of atherosclerosis, the apolipoprotein E knockout (ApoE KO) mouse. METHODS: Erectile function was evaluated by recording frequency-dependent increases in intracavernous pressure following electrical stimulation of the cavernous nerve in 26-, 32-, and 38-week-old ApoE KO mice fed a Western-type diet and age-matched C57BL6/J anesthetized mice. Atherosclerotic lesions were evaluated by planimetry in oil red O-stained aortas. RESULTS: We found that in contrast to C57BL6/J mice, ApoE mice displayed atherosclerotic lesions covering 22% of the aortic luminal surface at 26 weeks of age and increasing to 27% and 35% at 32 weeks and 38 weeks of age, respectively. The amplitude of erectile responses to electrical stimulation of the cavernous nerve was markedly impaired in 26-week-old ApoE KO mice as compared with age-matched C57BL6/J mice. Impairment in erectile function persisted in ApoE KO mice 32 and 38 weeks of age. CONCLUSIONS: The ApoE KO mouse, a well-characterized model to study disorders associated with hypercholesterolemia and atherosclerosis in cardiovascular research, could therefore be suitable for investigation of disease-modifying effects of new therapeutic strategies aiming to target both atherosclerosis and ED.

Animals↗
PubMed2005

D2-like receptors mediate the expulsion phase of ejaculation elicited by 8-hydroxy-2-(di-N-propylamino)tetralin in rats.

The mechanism of action by which 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) facilitates ejaculation in conscious rats is not clearly established. The serotonin (5-HT) 1A agonist 8-OH-DPAT may actually act on cerebral dopaminergic receptors to exert its proejaculatory effect. The present work was undertaken to clarify this issue by testing various compounds i.c.v. delivered in an experimental model of the expulsion phase of ejaculation in anesthetized Wistar rats. Intracerebroventricular delivery of 8-OH-DPAT dose-dependently (ED(50) = 17 microg) induced rhythmic contractions of bulbospongiosus (BS) muscles, which are of paramount importance for the expulsion of semen, occurring in the form of cluster of bursts evidenced by the recording of BS muscle electrical activity. The 5-HT1A antagonist WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide) (20 microg) i.c.v. coadministered with 8-OH-DPAT (20 microg) was unable to inhibit the effect of 8-OH-DPAT on BS muscle contractile activity. Conversely, raclopride (40 microg) and spiperone (10 microg), both dopamine D2-like receptor antagonists, i.c.v. coinjected with 8-OH-DPAT (20 microg), abolished BS muscle contractions. The involvement of D2-like receptors was further supported by the fact that the D2-like agonist quinelorane (20 microg i.c.v.) also induced BS muscle rhythmic contractions. Our data demonstrate that D2-like receptors mediate the induction by 8-OH-DPAT of rhythmic BS muscle contractions and suggest that i.c.v. delivery of D2-like receptor agonists to anesthetized rats represents a relevant experimental model to study the expulsion phase of ejaculation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2005

Identification of androgen receptors in the motoneurons of the external urethral sphincter in the spinal cord of female rats.

OBJECTIVES: In women, aging is associated with profound hormonal changes. Menopause has been implicated in the etiology of urinary tract complaints including incontinence, urgency and recurrent urinary tract infections. However, the use of hormone replacement therapy for these conditions has given conflicting and disappointing results. The role of androgen changes on urinary continence in perimenopausal women has not been studied. We studied the presence of androgen receptors in pudendal motoneurons controlling the external urethral sphincter of female rats. MATERIALS AND METHODS: A combination of retrograde labeling of pudendal motoneurons from the external urethral sphincter and immunohistochemistry for the N-terminal portion of androgen receptors on spinal cord sections was performed in adult female rats. RESULTS: Androgen receptors were identified in the nuclei of the ventral horn of the L5-L6 spinal cord. Pudendal motoneurons, retrogradely labeled from the external urethral sphincter, were identified in the dorsolateral nucleus of the ventral horn at the same levels. Confocal microscopy demonstrated the presence of nuclear and cytoplasmic androgen receptors in the cell bodies of these retrogradely labeled pudendal motoneurons. CONCLUSION: Our study demonstrated the presence of androgen receptors in the cell bodies of retrogradely labeled pudendal motoneurons controlling the urethral sphincter of female rats suggesting a role of androgens in the neuromodulation of urethral sphincter function at the spinal level.

Animals↗
PubMed2005

Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis.

OBJECTIVES: Sildenafil is a widely-prescribed effective on-demand treatment of erectile dysfunction (ED). Chronic treatment with sildenafil could help patients with ED. METHODS: The effects of an 8-week long treatment with sildenafil (60 mg/kg/d sc) in male Sprague Dawley rats were evaluated on electrically-elicited erectile responses in vivo before and after an acute injection of sildenafil (0.3mg/kg iv). In addition, endothelium-dependent and -independent relaxations of strips of corpus cavernosum in vitro were examined. All experiments were performed 36 hours after the last injection of sildenafil. RESULTS: Endothelium-dependent relaxations of cavernosal strips to acetylcholine were enhanced after chronic treatment with sildenafil while relaxations to A23187 or sodium nitroprusside were unchanged. Frequency-dependent erectile responses elicited by cavernous nerve stimulation were significantly improved. Moreover, the erectile responses to acute sildenafil were greater in chronically-treated rats with sildenafil. CONCLUSIONS: This is the first report providing experimental support for chronic dosing with sildenafil which could be of use for patients that are poor responders to on-demand treatment. Chronic sildenafil may regulate the transduction pathway leading to the activation of eNOS but has no effect on NO bioavailability or on the cGMP pathway, thereby eliminating a possible concern for tachyphylaxis.

Animals↗
PubMed2005

Physiology of ejaculation: emphasis on serotonergic control.

Ejaculation is constituted by two distinct phases, emission and expulsion. Orgasm, a feature perhaps unique in humans, is a cerebral process that occurs, in normal conditions, concomitantly to expulsion of semen. Normal antegrade ejaculation is a highly coordinated physiological process with emission and expulsion phases being under the control of autonomic and somatic nervous systems respectively. The central command of ejaculation is located at the thoracolumbar and lumbosacral levels of the spinal cord and is activated by stimuli from genital, mainly penile, origin although cerebral descending pathways exert both inhibitory and excitatory regulatory roles. Cerebral structures specifically activated during ejaculation form a tightly interconnected network comprising hypothalamic, diencephalic and pontine areas. A rational neurobiological approach has led to identify several neurotransmitters contributing to the ejaculatory process. Amongst them, serotonin (5-HT) has received strong experimental evidences indicating its inhibitory role in the central control of ejaculation. In particular, 5-HT1A cerebral autoreceptors but also spinal 5-HT1B and, in a lesser extent, 5-HT2C receptors have been shown to mediate the effects of 5-HT on ejaculation. Pharmacological strategies, especially those targeting serotonergic system, for the treatment of ejaculatory disorders in human will undoubtedly benefit from the application of basic and clinical research findings. In this perspective, the use of selective serotonin reuptake inhibitors (SSRIs) which basically increase the amount of central 5-HT and delay ejaculation in humans seems promising.

Central Nervous System↗