Vasomax for the treatment of male erectile dysfunction

This paper reviews laboratory and clinical data concerning oral phentolamin e mesylate, Vasomax, an alpha -1, alpha -2 adrenergic receptor antagonist d eveloped specifically for treatment of erectile dysfunction. A contemporary view of the neurovascular mechanisms in penile erection includes the effec ts of both smooth muscle relaxation and contraction. Contraction of the cav ernosal arteries and trabecular smooth muscle appears to be predominantly u nder the control of alpha -adrenergic innervation. Conversely, adrenergic b lockade of alpha -1 and alpha -2 receptors has been shown to facilitate pen ile erection in both animal and human models. The pharmacokinetic profile o f Vasomax appears well suited for an oral erectogenic agent. Vasomax is rap idly absorbed and eliminated in normal males. Peak plasma concentrations ar e achieved in 30-60 min, and the half-life approximates 5-7 h. Food decreas es the rate, but not the extent of bioavailability. Vasomax has low protein binding and is excreted primarily via urine and feces. There is a strong d ose-response relationship in maximum plasma concentration (Cmax) and area u nder the curve (AUC), and there are no clear age-related differences in abs orption or elimination rates. Efficacy of Vasomax has been systematically e valuated in two (ZON300, ZON301) large-scale, placebo-controlled trials, in addition to two long-term open-label studies. In both studies, Vasomax was associated with significant improvements in the erectile function domain s cores of the International Index of Erectile Function (IIEF). Further impro vements were noted as the duration of treatment and dose level were increas ed. The percentage of successful penetration attempts was also significantl y improved with Vasomax compared to placebo. For patients who continued in open-label treatment with Vasomax, efficacy was generally well maintained. Vasomax was well tolerated by the majority of patients. The most common sid e effects observed were nasal congestion (10%), headache (3%), dizziness (3 %), tachycardia (3%) and nausea (1%). Side effects were generally dose-rela ted and in the mild-to-moderate range in all three studies. Furthermore, si de effects seldom resulted in treatment discontinuation. Very few serious a dverse events were observed in these trials. In summary, Vasomax appears to be effective in the treatment of male erectile dysfunction and well-tolera ted by the majority of patients. The drug has a satisfactory side effect pr ofile, without significant risk of cardiovascular effects. Results of clini cal trials with Vasomax support the concept of adrenergic-blockade as a cli nically relevant mechanism in the control of penile erection.