Premature ejaculation - potential role of α2-adrenoceptor agonists for symptomatic treatment. Studies of dexmedetomidine, fadolmidine and tasipimidine

Abstract

Ejaculation is a physiological process that results in the expulsion of semen from the male reproduction tract during a sexual climax and is considered an essential component of natural conception. Ejaculation is a delicately orchestrated process controlled by the peripheral nervous system and the central nervous system and involving sympathetic, parasympathetic and somatic neurons. The most common ejaculatory dysfunction is premature ejaculation being also the most common sexual dysfunction in men – with a prevalence rate up to 30% and not much affected by age. Premature ejaculation is associated with reduced satisfaction in sexual life, distress, anxiety, and depression and has a negative impact on relationships with sexual partners. The etiology of premature ejaculation is considered multifactorial, with psychological, relationship and biological factors. There are limited pharmacological treatment options available. Dapoxetine, an on-demand selective serotonin uptake inhibitor, is the first drug registered for premature ejaculation treatment. A locally administered eutectic mixture of prilocaine/lidocaine, a spray with a local anesthetic effect on the penis, is the other approved medication for premature ejaculation, while others have been used as off-label. Clinical data accumulated in recent years suggests that lifelong premature ejaculation may be associated with increased activity of the sympathetic nervous system. Selective α2-adrenoceptors have a key role in regulating sympathetic tone in both the periphery and the CNS. Compounds that activate α2-adrenoceptors decrease sympathetic tonus, and they are widely used in human and veterinary practice. This knowledge of pharmacology prompted us to study the role of α2-adrenoceptor agonists dexmedetomidine, fadolmidine and tasipimidine in the symptomatic treatment of premature ejaculation. Our observations suggest that centrally acting α2-adrenoceptor agonists might provide symptomatic relief for premature ejaculation by prolonging ejaculation latency without affecting any other parameter of sexual behaviour or sexual incentive motivation. Whether the effects observed in male rats are directly transferrable to men can only be determined through clinical studies.