Targets for the treatment of erectile dysfunction: is NO/cGMP still the answer?

In recent years male sexual research has increasingly centered on molecular mechanisms operating from the central nervous system to peripheral end-organ levels involved in the penile erectile response. Major progress has been made in the field, and currently a whole host of neurotransmitters, chemical effectors, growth factors, second-messenger molecules, ions, intercellular proteins, and hormones have been characterized as components of the complex physiology of erectile function. Foremost among these mediators is nitric oxide (NO), which was initially characterized as a locally released physiologic mediator of the erectile response. Impaired formation and action of NO is closely associated with erectile dysfunction (ED), which may be caused by a variety of pathogenic factors. The impact of this knowledge has been substantial, leading to the development of several NO-based medical approaches for the treatment of ED. This review will focus on recent patents and current clinical trials involving innovative pharmacological and gene therapies in the field of male ED, particularly targeting the NO/intracellular cyclic GMP pathway, which still represents the most promising therapeutic approach to treat patients with ED.