Their extensive review begins with the present 3 approved PDE5 inhibitors in the USA: sildenafil, vardenafil and tadalafil. Although onset and duration of effects differ, all seem to provide about 65% erectile response compared to 32% for placebo. Side effect profiles for these three are similar and include headache, flushing, GERD, nasal congestion and visual disturbances. Tadalafil may also cause some myalgia and back pain.

Dopamine receptor agonists (apomorphine), given sublingually or intranasally (IN), improved ED (45 ? 51%) over placebo (33%) in multi-center studies. They seem especially useful in men with some preservation of erectile function. Side effects include nausea, headache and dizziness. They summarize by stating that ?The exact role of this agent is yet to be defined.?

Melanocortin receptor agonists must be given IN or subcutaneously (SQ). Erections occurred in 85% of men given SQ dosages, compared to 5% for placebo. Men also noted increased sexual desire. However, nausea (38%) and ?stretching and yawning? (56%) constituted notable side effects.

Alpha-adrenoceptor antagonists such as oral phentolamine mesylate remain under investigation, but investigators report concern with development of brown fat hyperplasia in treated animals. Other related agents under testing include alpha-adrenoceptor combinations with L-arginine, or the joining of injectable vasoactive intestinal polypeptide and phentolamine (approved in Denmark, New Zealand and the UK).

Topical prostaglandin-E1 may be applied transdermally. One controlled trial revealed 75% effectiveness compared to placebo response of 17%. Most men, however, experienced ?mild and brief? discomfort at the gel application site. Further studies continue.

Other agents in line for development and use include potassium channel openers, Rho-Kinase inhibition, vascular endothelial growth factor (VEGF) and nitric oxide (NO) synthase. As of this review, their effects in animals appeared encouraging.

The authors point out that combined therapies offer significant potential advantages: dose reduction with fewer side effects and potential improved ease of administration. They conclude by stating: ?The refinement of the many routes of administration and many novel agents with different mechanisms of action presents significant promise for combined therapy.?

BJU Int. 2003;92:534-538