Up until a few years ago, pharmacologic treatment of erectile dysfunction (ED) was limited to a few substances, most of which had to be injected directly into the corpora cavernosa. The oral substances available to treat erectile dysfunction included drugs containing yohimbine, and in some special cases the serotonin re-uptake inhibitor trazodone, officially approved for the indication of depression, and occasionally administered in an off-label use for erectile dysfunction (ED). There was also a plethora of aphrodisiacs or sexual tonics available, which usually contained a mixture of various substances, such as testis sicca, testosterone, yohimbine, ginseng, caffeine, barbituric acid, saw palmetto, cayenne fruit, and many others, in one preparation. Meanwhile many of these preparations disappeared from the market; some, however, are still available, in particular via the internet.

These include a range of drugs which contain yohimbine, vitamins (in particular vitamin E and vitamin B complex), dried extracts of muirapuama, gingseng and other herbal and plant extracts, or bamethan sulfate and benzyl nicotinate, respectively.

Common to all these aphrodisiacs, offered mostly by mail order sex companies or in sex shops, is the fact that their efficacy was never proven in well-designed placebo-controlled and double-blind clinical trials, and that only the belief in them may contribute to their promised efficacy, but not the usual homeopathic doses of the various compounds contained in these aphrodisiacs.

This site on pharmacologic treatment deals with all those substances, which have been clinically tested in a variety of erectile dysfunction studies and/or were finally approved in the indication of erectile dysfunction, at least in some countries of the world. In addition to drugs officially approved by the health authorities, this site also touches briefly on those medications/substances with which clinical studies in the indication of erectile dysfunction were conducted and reported in the literature, and which may be available in some countries, although not officially be approved for erectile dysfunction treatment.


Apomorphine SL

Phosphodiesterase-5 Inhibitors: Sildenafil (Viagra), Tadalafil (Cialis) and Vardenafil (Levitra)

Other Oral Drugs Used but not Approved for erectile dysfunction


Trazodone, approved for the treatment of depression, is a centrally-acting, selective serotonin re-uptake inhibitor, which inhibits cerebral serotonin turnover. Trazodone’s alpha-adrenoceptor blocking properties are a further important function of trazodone in relation to its erection-inducing effect. Both Saenz de Tejada et al. and Azadzoi et al. demonstrated that trazodone inhibits contraction of the cavernous smooth muscle, i.e. it facilitates relaxation..

It is still unclear which of the two effects (serotonin re-uptake inhibition orblocking of alpha-adrenoceptors) is more important with respect to the erection-inducing properties of trazodone. The success rates of trazodone in placebo-controlled trials were up to 67% vs. 39%forplacebo.

Side effects occur relatively often during trazodone treatment and may be attributed to its cerebral effects, via interference with serotonin metabolism, and to its peripheral, anti-adrenergic properties. The most common side effects described so far are marked fatigue and sleepiness, headache, dizziness, fall in blood pressure and nausea. Patients find the marked fatigue and dizziness particularly troublesome and they are the mostly the cause for premature discontinuation rates in 20-30% of cases (130, personal experience).


In the era of very successful PDE-5 inhibitors the only indication for an attempt with trazodone appears to be the constellation of psychogenic erectile dysfunction and concomitant depression. In this regard it has to be mentioned that the literature contains reports of more than 200 cases of priapism associated with trazodone therapy.

Phentolamine (Vasomax ®)

Phentolamine is a competitive, non-selective alpha1-and alpha2-adrenoceptor antagonist, which blocks both presynaptic and postsynaptic alpha-adrenoceptors. This explains its general cardiovascular effects, such as lowering of blood pressure. Its proerectile effects, when injected directly into the cavernous bodies, were described by several authors. The real breakthrough for phentolamine came when it was successfully used along with papaverine for intracavernous self-injection therapy, which is still in place to date. The same author described successes in 21 out of 69 cases (30%), with a new buccally-administered preparation of phentolamine (20mg).

Phentolamine mesylate in tablet form for oral administration was developed by Zonagen, and has been tested for efficacy and safety between 1995 and 1997 in three large multicenter studies in Germany, Mexico and the USA.

Oral phentolamine was temporarily approved in some countries of South America in 40 mg tablets, but was withdrawn early from the market due both to its very limited efficacy, and to the fact that the FDA refused its approval in the US because it was said to induce brownish discoloration of the fat tissue in rats.


L-arginine is the precursor of NO synthesis. Zorgniotti et al. conducted a placebo-controlled study with 2800mg L-arginine per day in 20 impotent men for two weeks. Of the 15 men who completed the study, six reported an improvement in the ability to achieve an erection, nine experienced no improvement.

In a placebo-controlled, crossover study on 21 patients with erectile dysfunction of different etiology, the efficacy of 500mg L-arginine applied three times daily, was tested over a period of twice 17 days without showing a superiority over the placebo.

A high-dose, prospective, randomized, double-blind and placebo-controlled study with 5 g L-arginine per day for six weeks was conducted in 50 patients (aged 55-75 years) with organic, complete erectile dysfunction (unable to perform coitus), for at least six months. This study resulted in success rates (sexual intercourse possible) of 31% in the L-arginine group, compared to 12% in the placebo group. It was interesting to note that significantly higher urine concentrations of the stable NO metabolites, N02 and N03, were measured in the arginine responders than in the non-responders, although the responders had lower urine concentrations of N03 prior to treatment. Thus the question arises as to whether supraphysiologic doses of L-arginine given over a long period of time can lead to a permanent improvement in cavernous function in some of the erectile dysfunction patients. No side effects were observed, except a fall in blood pressure of maximum 10% in some patients, which did not result in clinical symptoms.

Gingko biloba extract

In a prospective, double-blind and placebo-controlled study in 32 patients, the efficacy of gingko biloba was evaluated over a period of 24 weeks. Gingko biloba did not result in a subjective, or a statistically significant objective (NPT testing) — improvement of erection.

Korean red ginseng

In a three arm, placebo-controlled study with trazodone, placebo or ginseng in 90 patients (30 in each arm), global efficacy rates of 60% (p < 0.05) were reported for ginseng and 30% for both placebo and trazodone. The erection-promoting effect of ginseng is attributed to its saponin content, although its exact mechanism of action is unclear.

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