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Central Versus Vascular: Why This Is Not a PDE5 Inhibitor
The most important conceptual contrast is between bremelanotide and phosphodiesterase-5 (PDE5) inhibitors such as sildenafil and tadalafil. PDE5 inhibitors act peripherally: they prevent the breakdown of cyclic GMP in the smooth muscle of the corpus cavernosum
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- The most important conceptual contrast is between bremelanotide and phosphodiesterase-5 (PDE5) inhibitors such as sildenafil and tadalafil. PDE5 inhibitors act peripherally: they prevent the breakdown of cyclic GMP in the smooth muscle of the corpus cavernosum, enhancing the vasodilation that produces an erection once arousal has already begun. They do essentially nothing to generate desire; they facilitate the plumbing of an arousal that must be initiated by other means.
- Bremelanotide operates one level upstream. By engaging central melanocortin and dopaminergic circuits, it targets the origination of sexual motivation itself. This is why the two mechanisms are complementary rather than redundant, and why bremelanotide has been of interest for desire disorders (where the deficit is in wanting) whereas PDE5 inhibitors address performance disorders (where the deficit is in physical response). The two are compared in detail later in this article.