Morales A
Kingston General Hospital, Ontario, Canada.
World J Urol. 2001 Aug;19(4):251-5. doi: 10.1007/s003450000182.
The systemic use of adrenergic antagonists in the treatment of sexual dysfunction has originated more controversy than results. Among the various agents, yohimbine has acquired an unenviable reputation in the treatment of erectile dysfunction. The drug is pharmacologically well characterized as an alpha2 adrenoceptor antagonist with activity in the central and peripheral nervous systems. In-depth, systematic studies in animals have shown that yohimbine has a remarkable positive effect on sexual performance. Meta-analyses of the few controlled, randomized human studies have consistently shown an advantage of yohimbine over placebo. Despite such a long history and encouraging activity, the drug has not yet been subjected to scientifically rigid human clinical trials. Although relevant basic pharmacological and animal research information has been available for over 15 years, recent studies have been designed with a lack of insight and complete disregard of those fundamental studies. Currently, dose-response investigations are not available, alternative routes of administration (i.e., sublingual) have not been investigated, nor has continuous versus "on-demand" administration been explored. Synergistic activity with other drugs was last studied nearly four decades ago. Assessments of various populations were carried out in very limited cohorts and only in the most general terms. In short, properly designed trials in humans have not been performed. This apparent lack of scientific and financial interest has various roots. First of all, yohimbine is an old drug. As such it does not enjoy patent protection or commercial viability. Until molecular/formulation changes can be brought about (as recently happened with two other venerable agents: phentolamine and apomorphine) serious investigation of the drug will remain in limbo. Another promising avenue is the potential for synergistic effect of yohimbine with other compounds. When all is said and done, it could be that the naysayers are right and yohimbine indeed lacks clinical activity as a treatment for the phallodynamically challenged. As long as it remains an orphan drug we will never know. One hopes that interest can be eventually generated for the proper assessment of yohimbine in a different formulation or in combination with other agents.
在性功能障碍治疗中全身使用肾上腺素能拮抗剂引发的争议多于取得的成果。在各种药物中，育亨宾在治疗勃起功能障碍方面名声不佳。该药在药理学上被明确为一种α2肾上腺素能受体拮抗剂，在中枢和外周神经系统均有活性。对动物进行的深入、系统研究表明，育亨宾对性行为表现有显著的积极作用。对少数对照、随机的人体研究进行的荟萃分析一致显示，育亨宾优于安慰剂。尽管有如此悠久的历史和令人鼓舞的活性，但该药尚未经过严格的人体科学临床试验。虽然相关的基础药理学和动物研究信息已存在超过15年，但最近的研究设计缺乏洞察力，完全忽视了那些基础研究。目前，尚无剂量反应研究，未对替代给药途径（即舌下给药）进行研究，也未探讨持续给药与“按需”给药的差异。与其他药物的协同活性上一次研究是在近四十年前。对不同人群的评估仅在非常有限的队列中进行，且只是最笼统的评估。简而言之，尚未开展设计合理的人体试验。这种明显缺乏科学和资金投入兴趣的情况有多种根源。首先，育亨宾是一种老药。因此它没有专利保护或商业可行性。除非能实现分子/剂型改变（就像最近另外两种老牌药物：酚妥拉明和阿扑吗啡那样），否则对该药的认真研究将一直停滞不前。另一个有前景的途径是育亨宾与其他化合物产生协同效应的可能性。说到底，可能持反对意见者是正确的，育亨宾作为治疗阴茎动力学障碍的药物确实缺乏临床活性。只要它仍然是一种孤儿药，我们就永远无法知晓。人们希望最终能激发兴趣，对不同剂型或与其他药物联合使用的育亨宾进行恰当评估。
