The development of selective inhibitors of phosphodiesterase (PDE) 5 and introduction of these compounds as effective, safe and well-tolerated orally active drugs for the treatment of erectile dysfunction (ED) has become a world-wide clinical and pharmaceutical success and also brought further attention to the physiological mechanisms involved in the control of normal male sexual function. This includes both peripheral intracellular signal transduction in the penis as well as central brain and spinal cord pathways controlling penile erection. Increasing knowledge of intracellular signal propagation in cavernous smooth muscle tone regulation has provided the basis for identifying new and more selective pharmacological approaches to manage ED. As a consequence, beyond the PDE5 inhibitors sildenafil, vardenafil and tadalafil, the potential use of several new drugs acting via different pathways in the treatment of ED is now being discussed. A brief overview is given on the status of specific compounds that could become important in the future oral pharmacotherapy of male ED.
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