Emerging drugs for premature ejaculation.

Lifelong premature ejaculation (PE) is a frequent male sexual dysfunction and is thought to be mediated in part by disturbances of serotonergic (5-hydroxytryptamine; 5-HT) neurotransmission and ejaculation-mediating 5-HT receptors in the CNS. The aetiology of the dysfunction is unclear, but probably includes neurobiological and environmental factors. Lifelong PE is a syndrome characterised by a cluster of symptoms. Rapid ejaculations become manifest around the first sexual encounters in puberty or adolescence. Intravaginal ejaculation latency time usually occurs within 30-60 s, or maximally within 2 min after vaginal penetration, is present with nearly every sexual partner, and remains similar throughout life or may aggravate during ageing. The syndrome may lead to secondary psychological, sexual and relationship problems. Daily treatment with some selective serotonin re-uptake inhibitors (SSRIs) leads to strong ejaculation delay, but may be accompanied by side effects. New treatment with SSRIs with a short half-life (if approved) for on-demand use 1-2 h prior to coitus exerts less ejaculation-delaying effects than daily SSRI strategies. Animal studies have shown that strong, immediate ejaculation delay may be induced by the combination of an SSRI with a 5-HT(1A) receptor antagonist. The combination of an SSRI and any other compound that immediately strongly raises 5-HT neurotransmission may form the basis for the development of new on-demand drugs to treat PE.