Mode of action
The sympathetic nervous system normally maintains the penis in a flaccid or non-erect state. All of these vasoactive drugs, when injected into the corpora cavernosae, inhibit or override sympathetic inhibition to encourage relaxation of the smooth muscle trabeculae within the penile erectile bodies. The ensuing onrush of blood engorges the penile corpora cavernosae sinusoidal spaces with sufficient pressure to compress the emissary veins that normally drain blood from the penis. The combination of accelerated arterial inflow and impeded venous outflow from the corpora cavernosae creates an erection.

Specific Drugs

Papaverine
Papaverine is a nonspecific phosphodiesterase inhibitor that increases cyclic AMP and cyclic GMP concentrations in penile erectile tissue. The usual dose ranges from 15 to 60 mg. Given in doses of 7.5-90 mg, initially alone and later with phentolamine as a synergist in the ratio of 30:1, these treatments did not have a product licence but they were effective (up to 80 percent in men with psychogenic and neurogenic erectile dysfunction, but is less effective in men with vasculogenic dysfunction,36 to 50 percent), cheap, stable at room temperature and easy to use. Its major disadvantages are priapism (in up to 35 percent of cases), corporal fibrosis (in up to 33 percent of cases), and occasional increases in serum aminotransferase concentrations. Currently, the use of isolated papaverine is not routinely used because of its unacceptably high complication rates, like priapism and systemic effects. However, its most frightening effect is corpora cavernosa fibrosis, which can occur even after a single injection.

Phentolamine
Phentolamine is a competitive -adrenergic-receptor antagonist. When used alone, phentolamine does not produce rigid erections; when it is combined with papaverine, success rates range from 63 to 87 percent. A combination of 30 mg of papaverine and 0.5 to 1 mg of phentolamine is typically used, and the usual dose ranges from 0.1 to 1 ml. The side effects of phentolamine include hypotension and reflex tachycardia.

Alprostadil (prostaglandin E1)
Alprostadil (prostaglandin E1) was given a product licence in 1994 and is supplied in 5, 10, and 20 µg doses.

Alprostadil (prostaglandin E1)'s efficacy is superior to that of papaverine and the combination of papaverine and phentolamine; it results in erections in more than 79 % of men. In addition, alprostadil is associated with a relatively low incidence of priapism (0.35 to 4 percent) and fibrosis (1 to 23 percent). Additionally, thanks to its rapid intracavernosal metabolization, priapism occurrence is lower than 1%, and the onset of corpora cavernosa fibrosis caused by prostaglandin is not frequent. The most important side effect is pain in the injection site, which occurs in up to 40% of patients. This pain, strongly intense, can last up to 3 hours after the injection, and is the main cause of treatment voluntary-cessation.

A six month study investigated the efficacy and safety of a program of at-home intrapenile alprostadil injections. Six hundred and eighty three men with vasculogenic, neurogenic, psychogenic, and mixed causes of erectile dysfunction entered the trial and 471 (69 percent) completed the trial. The reasons for drop out included penile pain, lack of efficacy, loss to follow-up, dislike of self injection, and other problems. Sexual activity, recorded as sexual intercourse or masturbation, was reported by 551 men over the six-month period.

A total of 11,223 instances of sexual intercourse and 701 masturbatory episodes occurred after 13,762 intrapenile alprostadil injections. This pattern of sexual activity was deemed to be satisfactory by 87 percent of the men completing the trial and 86 percent of their partners.

Despite the relatively high success rate, there is a very high attrition rate with self-injection when used long-term, suggesting that ICI may not be a satisfactory long term treatment for many men.

Other Drugs
Recently, another unique formulation of alprostadil with an alpha-cyclo dextrin ring (called alprostadil alphadex) has been approved by the U.S. FDA for use. This formulation tends to be more heat-stable and effective over a wide variety of doses, ranging up to 40 mcg. The vast majority of patients who use it achieve an excellent erection and high level of partner satisfaction.

Vasoactive intestinal polypeptide (VIP), 0.025 mg in combination with phentolamine (1 mg or 2 mg), is awaiting a licence, and there have been early reports of success from trials.