Opportunities for the treatment of erectile dysfunction by modulation of the NO axis--alternatives to sildenafil citrate.

Erectile function in man depends upon a complex interaction of psychogenic, neurologic, hormonal and vascular factors, and therefore the management of erectile dysfunction (ED) reflects this complexity of control. Therapeutic options include psychological and non-pharmacological approaches as well as drug treatments. The effectiveness of the type-5 cGMP phosphodiesterase inhibitor sildenafil citrate (Viagra) confirms the pivotal role of the NO-cGMP axis in promoting and maintaining erection. Although widely acclaimed, sildenafil leaves many questions unanswered, especially regarding its susceptibility to pharmacokinetic drug interactions, and its safety in patients with ischaemic heart disease and those taking nitrates. In view of the epidemiological link between erectile dysfunction and cardiovascular disease in the elderly, this limitation might have much broader implications. The presently available scientific documentation, although less extensive, indicates that NO donors, such as topically applied nitroglycerin (GTN; for example, 1-2 puffs of an ordinary GTN spray applied to the shaft of the penis), might be a reasonable alternative. Further larger-scale research on the efficacy and tolerability of topical GTN is needed to establish its full therapeutic potential in the treatment of erectile dysfunction.