Treating men with predominantly nonpsychogenic erectile dysfunction with intracavernosal vasoactive intestinal polypeptide and phentolamine mesylate

This multicenter, randomized, double-blind clinical trial evaluated the combination of aviptadil (vasoactive intestinal polypeptide, VIP, at a dose of 25 mcg) with phentolamine mesylate (1-2 mg) administered by intracavernosal injection for the treatment of predominantly nonpsychogenic erectile dysfunction (ED). The study included 236 men across multiple European centers.

VIP is an endogenous neuropeptide of 28 amino acids with potent vasodilatory action, naturally released by nerve endings in cavernosal tissue during sexual arousal. The combination with phentolamine (an alpha-adrenergic blocker) potentiates the vasodilatory effect, facilitating relaxation of cavernosal smooth muscle and penile engorgement.

The results demonstrated an erectile response rate of 83.9% with the active combination, significantly superior to placebo. The median erection duration was 54 minutes, considered clinically adequate for sexual intercourse. The most common adverse events were transient facial flushing and mild injection site pain, both of mild intensity.

An important advantage observed was the absence of priapism (prolonged and painful erection), a relatively common side effect with intracavernosal prostaglandins (such as alprostadil) that were the standard of treatment at the time. This gave VIP/phentolamine a differentiated safety profile, although the need for intracavernosal injection limited its broad clinical adoption in favor of the oral PDE5 inhibitors that emerged around the same time.