New directions for erectile dysfunction therapies

Abstract

Research in the field of erectile function and dysfunction has continued to expand rapidly. Based on the information available, some directions for future erectile dysfunction therapies can be identified. The first direction is improvement of current therapeutic principles. A second generation of orally active phosphodiesterase (PDE) inhibitors is being introduced, and further developments within this field can be expected. The recent introduction of apomorphine has opened the way for new dopamine receptor agonists. The second direction is combinations of existing therapeutic principles. Combinations of apomorphine and sildenafil and apomorphine and a 1 -adrenoceptor (AR) antagonists, for example, seem attractive and may have a therapeutic potential in patients not responding satisfactorily to single-drug treatment. Nitrosylated a 1 -AR antagonists, combining nitric oxide donation and a 1 -or a 2 -AR antagonism, are currently being evaluated. The third direction is new targets within the central nervous system. Melanocortin receptor agonists have shown promise not only in animal models, but also in preliminary studies in humans. Other possible targets, such as growth hormone-releasing peptide receptors, are being explored. The fourth direction is new peripheral targets. Rho-kinase antagonism and non-nitric oxide-mediated stimulation of soluble guanylyl cyclase have been suggested as possible new principles for drug development. The fourth direction is gene therapy. Progress has been made in intracavernosal somatic gene therapy and will probably continue. Still, problems remain, and advantages over conventional pharmacological therapies have to be demonstrated. The final direction is prevention strategies. Strategies to prevent cavernosal degeneration and=or to restore cavernosal function will be one of the most exciting challenges for future research.

Time/duration effectiveness of sildenafil versus tadalafil in the treatment of erectile dysfunction in male spinal cord-injured patients

“…The development of the new PDE-5 inhibitors prompts the question of whether and how these three substances differ in terms of their efficacy and adverse effects for a specific category of ED, including SCI patients, allowing the best choice from these oral drugs. 19 Our results showed that the advantage of tadalafil over sildenafil in terms of duration of action was not influenced by level or degree of lesions in SCI men. In our study, two out of five patients (40%) not responding to sildenafil, all with LMN from lumbar incomplete lesions with minimum preservation of reflexive erection, reported to be satisfied after sexual intercourse using tadalafil.…”

Central Mechanisms Regulating Penile Erection in Conscious Rats: The Dopaminergic Systems Related to the Proerectile Effect of Apomorphine

“…The differences in these results may be explained by the differences in the doses used between the studies. A number of studies have also reported that in rats, dopamineinduced penile erection seems to involve, particularly, the D 2 -like receptor subtypes, and this seems to be the case also in humans (Heaton, 2000;Andersson and Hedlund, 2002). PNU-95666E is a centrally acting agonist that reportedly activates the D 2 receptor in central dopamine neurons, increases striatal acetylcholine concentrations, and decreases cerebellar nucleotides in rats and mice after systemic administration (Durhama et al, 1997;Heier et al, 1997;Sethy et al, 1997).…”

“…The central nervous system (CNS) is an attractive target for discovery of novel therapeutic approaches for the treatment of ED, and many potential sites for CNS-acting drugs have been hypothesized (Andersson and Hedlund, 2002). Pharmacological experiments have focused on the role of neurotransmitters and neuropeptides involved in the central control of erection, via spinal and supraspinal pathways (Andersson, 2001).…”

Preclinical effects of melanocortins in male sexual dysfunction

“…Although the D2 receptor family seems to be responsible for most of the behavioral effects of dopamine, D1 receptors also may play a role in sexual response. 11 Rodent studies have concluded that dopamine is involved in anticipatory rather than in consummatory motivational sexual responses. Quail models have proposed that dopamine activates a-2-noradrenergic receptors in the MPOA.…”