Prosexual Effects Research Articles

The first reported UK fatality related to gamma-butyrolactone (GBL) ingestion

Gamma-butyrolactone (GBL) is rapidly metabolized to gamma-hydroxybutyrate (GHB) in vivo following ingestion. GBL and GHB cause similar clinical features in users, and both of these agents are widely used as recreational drugs due to their mood-enhancing, stimulant and prosexual effects, particularly on the nightclub scene.1,2 In 2003, GHB was classified in the UK as a Class C controlled substance under the Home Office Misuse of Drugs Act (1971). GBL is currently not classified in the UK and many other countries in the world; the UK Home Office Advisory Council on the Misuse of Drugs is currently consulting on proposed changes to the legal status of GBL, and the related compound 1,4-butanediol (1,4BD). There are numerous reported fatalities related to GHB ingestion.3 However, although there has been media coverage in the lay press of potential GBL-related fatalities in the UK,4,5 there have only been three previous reports of GBL-related fatality, two in Germany and one in the USA.6,7 We report here the first case of a fatality related to isolated GBL toxicity in the UK, which we feel supports the case for classifying GBL similar to that of GHB.

Turnera diffusa Wild (Turneraceae) recovers sexual behavior in sexually exhausted males

Ethnopharmacological relevance In folk medicine , Turnera diffusa Wild ( Turnera diffusa, Turneraceae) is considered as an aphrodisiac, but its ability to restore copulation in sexually inhibited subjects has not been reported. Aim of the study To determine whether Turnera diffusa recovers sexual behavior in sexually exhausted (SExh) male rats and to identify the main components in an aqueous extract. Materials and methods SExh males were treated with Turnera diffusa, 20–80 mg/kg, yohimbine, 2 mg/kg, or vehicle. Results Yohimbine and Turnera diffusa (80 mg/kg) significantly increased the percentage of males achieving one ejaculatory series and resuming a second one. In addition, Turnera diffusa significantly reduced the post-ejaculatory interval. These effects were not associated to an increase in locomotor activity or anxiety-like behaviors. The HPLC–ESI-MS analysis showed the presence of caffeine, arbutine, and flavonoids as the main compounds in the active extract. Conclusion The results support the use of Turnera diffusa as an aphrodisiac in traditional medicine and suggest possible therapeutic properties of Turnera diffusa on sexual dysfunction. The flavonoids present in active extract may participate in its pro-sexual effect, which is analogous to those produced by yohimbine, suggesting a shared mechanism of action.

Clavulanic acid stimulates sexual behaviour in male rats

Sexual behaviour in rats can be used to predict putative effects on human sexual behaviour. Anecdotic reports exist, that the beta-lactamase inhibitor, clavulanic acid exerts sexual stimulating activities in monkeys. To characterize these pro-sexual activities, clavulanic acid was tested in three doses and compared to one dose of a sexually inhibitory dose of the selective serotonin reuptake inhibitor, paroxetine, in sexually-experienced male rats, selected for a moderate level of sexual performance in a standard 30-min test with an oestrus female. After acute administration, clavulanic acid had minor sexual stimulating effects at the highest dose in the number of intromissions and in the first ejaculation series. After sub-chronic 7-days treatment, clavulanic acid increased the number of ejaculations at all three doses and reduced the number of intromissions in the 1st series at the highest dose. After chronic 14 days treatment, a similar but stronger pro-sexual profile was observed. The sexual side effects of paroxetine were as expected, including slight sexual inhibitory effects after acute administration, but somewhat stronger overall inhibitory effects after 7 and 14-days pretreatment, particularly notable in the decreasing number of animals contributing to the 2nd ejaculation series, which was even stronger after 14-days treatment. One week after cessation of treatment, the paroxetine group had completely recovered, whereas the highest dose-group of clavulanic acid still showed some pro-sexual effects. This remarkable pro-sexual activity of clavulanic acid cannot readily be explained by its mechanism of action as a beta-lactamase inhibitor but could be due to unexpected central activity of the compound.

From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long‐term adverse consequences of drug use?

Addictive drugs can profoundly affect social behaviour both acutely and in the long-term. Effects range from the artificial sociability imbued by various intoxicating agents to the depressed and socially withdrawn state frequently observed in chronic drug users. Understanding such effects is of great potential significance in addiction neurobiology. In this review we focus on the 'social neuropeptide' oxytocin and its possible role in acute and long-term effects of commonly used drugs. Oxytocin regulates social affiliation and social recognition in many species and modulates anxiety, mood and aggression. Recent evidence suggests that popular party drugs such as MDMA and gamma-hydroxybutyrate (GHB) may preferentially activate brain oxytocin systems to produce their characteristic prosocial and prosexual effects. Oxytocin interacts with the mesolimbic dopamine system to facilitate sexual and social behaviour, and this oxytocin-dopamine interaction may also influence the acquisition and expression of drug-seeking behaviour. An increasing body of evidence from animal models suggests that even brief exposure to drugs such as MDMA, cannabinoids, methamphetamine and phencyclidine can cause long lasting deficits in social behaviour. We discuss preliminary evidence that these adverse effects may reflect long-term neuroadaptations in brain oxytocin systems. Laboratory studies and preliminary clinical studies also indicate that raising brain oxytocin levels may ameliorate acute drug withdrawal symptoms. It is concluded that oxytocin may play an important, yet largely unexplored, role in drug addiction. Greater understanding of this role may ultimately lead to novel therapeutics for addiction that can improve mood and facilitate the recovery of persons with drug use disorders.

Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors

Sexual dysfunctions such as low libido, anorgasmia, genital anesthesia, and erectile dysfunction are very common in patients taking selective serotonin reuptake inhibitors (SSRIs). It has been assumed that these side effects always resolve after discontinuing treatment, but recently, four cases were presented in which sexual function did not return to baseline. Here, we describe three more cases. Case #1: A 29-year-old with apparently permanent erectile dysfunction after taking fluoxetine 20 mg once daily for a 4-month period in 1996. Case #2: A 44-year-old male with persistent loss of libido, genital anesthesia, ejaculatory anhedonia, and erectile dysfunction after taking 20-mg once daily citalopram for 18 months. Case #3: A 28-year-old male with persistent loss of libido, genital anesthesia, and ejaculatory anhedonia since taking several different SSRIs over a 2-year period from 2003-2005. No psychological issues related to sexuality were found in any of the three cases, and all common causes of sexual dysfunction such as decreased testosterone, increased prolactin or diabetes were ruled out. Erectile capacity is temporarily restored for Case #1 with injectable alprostadil, and for Case #2 with oral sildenafil, but their other symptoms remain. Case #3 has had some reversal of symptoms with extended-release methylphenidate, although it is not yet known if these prosexual effects will persist when the drug is discontinued. SSRIs can cause long-term effects on all aspects of the sexual response cycle that may persist after they are discontinued. Mechanistic hypotheses including persistent endocrine and epigenetic gene expression alterations were briefly discussed.

Pro-ejaculatory effect of the aqueous crude extract of cihuapatli ( Montanoa tomentosa) in spinal male rats

In the present study, the pro-sexual effect of the cihuapatli ( Montanoa tomentosa) and its possible pro-ejaculatory properties in spinal male rats were examined. Systemic administration of the aqueous crude extracts of Montanoa tomentosa exerted a pro-ejaculatory effect and produced an increase in the number of discharges in the ejaculatory motor patterns in the spinal rats. The cihuapatli-induced ejaculatory responses included the expression of penile erections and penile movements and the potent expulsion of urethral contents and in some cases the expulsion of seminal plugs. The cihuapatli-induced ejaculatory motor patterns were similar to that obtained after systemic oxytocin. Cihuapatli- and oxytocin-induced ejaculatory motor responses and the penile erections and movements were abolished by the pre-treatment with hexamethonium, a selective oxytocin antagonist. Present data show that the cihuapatli extract acts directly at the spinal system in charge of the expression of the ejaculatory motor patterns and suggest that the aqueous crude extract exerts its aphrodisiacs properties by increasing sexual potency acting as an oxytocic agent.

Drug treatments for women's sexual disorders

This article is a review of the available evidence of prosexual effects of drugs for women's sexual disorders. Sexual function and its disorders in women are discussed with special emphasis on psychophysiological measures and the differentiation between sexual disorders. This discussion may serve to put in perspective the complexities of women's sexual response and possible drug effects. Searches in Medline and EMBASE resulted in finding many reports of prosexual effects. Substitution therapy in postmenopause is the only well documented treatment to relieve sexual problems. There is evidence from experimental studies for an influence on physiological sexual arousal, but not on subjective sexual experience of adrenergic compounds. Knowledge about prosexual effects in women of most other drugs is based on studies of augmentation therapies, or studies of doubtful design, and often reports about case studies with reliance only on subjective reports.

Effect of Bupropion-SR on Orgasmic Dysfunction in Nondepressed Subjects: A Pilot Study

The objective of this study was to determine whether the aminoketone antidepressant bupropion has beneficial effects in orgasmic dysfunction. Design: Single-blind, sequential treatment order of three weeks each: placebo, bupropion-SR 150 mg/day, bupropion-SR 300 mg/ day Subjects: Nondepressed women ( n = 20) and men ( n = 10) having nonphysiologic orgasmic delay or inhibition Main Outcome Measures: Reported difficulty or delay in achieving orgasm, satisfaction with orgasm and erectile function, and subjective impressions of drug effect Results: In the women, there were significant improvements relative to baseline ( p < .01) on both doses of bupropion-SR in all measured aspects of sexual function, and significant improvements relative to placebo ( p < .05) in overall sexual satisfaction on both doses and satisfaction with intensity of orgasm on 150 mg/day (300 mg/day, p = .10). In the men, significant improvements over baseline ( p < .01) were observed with both doses in overall sexual satisfaction, ability to achieve an erection, and delay in reaching orgasm/ejaculation; significant improvements relative to placebo ( p < .05) were observed in overall sexual satisfaction on both doses, ability to achieve erection on 150 mg/ day, and delay in orgasm/ejaculation on 150 mg/day. Seventy percent of subjects reported improvement in libido, arousal, or orgasmic function during bupropion administration. relative to placebo ( p < .05) were observed in overall sexual satisfaction on both doses, ability to achieve erection on 150 mg/ day, and delay in orgasm/ejaculation on 150 mg/day. Seventy percent of subjects reported improvement in libido, arousal, or orgasmic function during bupropion administration. Conclusions: Bupropion-SR may be a useful agent for treating orgasmic delay and inhibition, and possibly disorders of sexual arousal. The results argue against bupropion’s apparent prosexual effect in depressed patients being simply a result of its antidepressant activity.

Oxytocin and Female Sexuality

A search of the literature has been prepared to determine how oxytocin may affect sexual and reproductive in women. Many animal studies suggest that oxytocin induces a variety of reproductive behaviors, including grooming, sexual arousal, orgasm, gamete transport, nesting, birthing, and specific maternal behaviors such as breast-feeding and bonding between mother and infant. These actions are apparently facilitated by the 'priming' effect on certain cells by sex and steroid hormones - as the brief case report would also suggest. However, no adequate double-blind trial has confirmed the observations from this report in women. Only animal studies have been performed, albeit over a wide range of species. A variety of other causes and effects of sexual interest and arousal relating to oxytocin are considered, including some of those in males. More research is needed to clarify the role of oxytocin in human reproductive behaviors, including its potential 'aphrodisiac' or prosexual effect in women in the presence of the sex-steroid hormones.

Prosexual drugs: empirical status of the "new aphrodisiacs".

The search for an effective aphrodisiac has been a perennial pursuit of most societies throughout history. In the past decade, attention has focused increasingly on the prosexual effects of oral pharmacological agents with central neurotransmitter actions. The role of various dopaminergic, adrenergic, and serotonergic agents, in particular, has been intensively investigated in both human and animal studies. Some of these drugs have been considered for their potential role in the treatment of sexual dysfunction, while others have contributed to our understanding of basic neurophysiological processes in sexual arousal. This review provides a critical evaluation of current laboratory and clinical research on the "new aphrodisiacs," including studies in both patient populations and normal volunteers. Several conceptual and methodological problems are addressed, such as the definition and measurement of sexual response, the need to separate specific and nonspecific drug effects on sexual response, and the lack of studies in women. Although no single drug has proven to be clinically safe and reliably effective for human use, several promising candidates have been identified. Overall, research on prosexual drugs has contributed significantly to our understanding of basic mechanisms in sexual response, as well as providing new treatment options for common sexual disorders.

The classification of 5-hydroxytryptamine receptors.

1. The current classification of receptors for 5-hydroxytryptamine (5-HT) is based on functional studies, and encompasses three main receptor types. 2. 5-HT1-like receptors mediate inhibition of release of various neurotransmitters from central and peripheral sites, smooth muscle contraction and relaxation (and release of endothelium-derived relaxing factor), tachycardia, a variety of behavioural actions (for example, forepaw treading, hypothermia, hyperphagia, drug discriminative stimulus properties, nociceptive pathway modulation, and anxiolytic, anti-aggressive and prosexual effects), and central neuronal excitatory and inhibitory activity. Selective antagonists for this receptor are not yet available, but the 5-HT2 receptor antagonists methysergide and methiothepin have appreciable affinity for 5-HT1-like receptors, and 5-carboxamidotryptamine is a selective agonist. 3. 5-HT2 receptors mediate smooth muscle contraction, platelet aggregation, increased capillary permeability, some behavioural syndromes (for example, head twitch and wet-dog shakes) and drug discriminative stimulus properties, central neuroexcitatory effects, and some neuroendocrine functions. Ketanserin and cyproheptadine are selective antagonists. 4. 5-HT3 receptors mediate peripheral afferent and efferent neuroexcitatory actions, anxiogenic effects, and modulation of cytotoxic drug-induced emesis, gastric emptying, and dopamine-related mesolimbic hyperactivity. Selective antagonists include cocaine, MDL 72222 and ICS 205-930; 2-methyl-5-HT is a selective agonist.