Calabro RS, Polimeni G, Bramanti P. Recent advances in the treatment of neurogenic erectile dysfunction. Recent Pat CNS Drug Discov 2014;9(1):41-53. http://www.eurekaselect.com/120103/article
Neurogenic erectile dysfunction (ED) can be broadly defined as an inability to sustain or maintain a penile erection owing to a neurological impairment, either centrally or peripherally or both.
Although significant advances in the pharmacological treatment of ED have occurred in recent years, especially after the introduction of oral selective phosphodiesterase type 5 inhibitor, the treatment of neurological patients with ED may be challenging for prescribers, given poor data available on this topic and the variety of etiologic factors (iatrogenic, endocrine, psychiatric and psychosocial) to consider. At the same time, several, new oral, local and surgical treatments are available and their efficacy and safety depend on the specific cases.
This review provides a comprehensive and updated description of current and future ED therapies, including assigned patents, with a special focus on the treatment of neurogenic erectile dysfunction.
Phentolamine induces relaxation of cor-pus cavernosum erectile tissue mainly by blocking both 1
and 2 adrenergic receptors . To date, its effectiveness
and safety in ED management, at an oral dose of 40-80 mg,
has been suggested in limited studies .Yohimbine
Yohimbine facilitates erection by blocking
central 2 adrenergic receptors and produces an increase in
sympathetic drive and firing rate of neurons within the brain
noradrenergic nuclei. The drug (up to 6 mg) seems to be su-perior to placebo in the treatment of ED, although, overall,
available results on treatment are not impressive [41, 42].
We have to underline that adrenergic centrally acting
agents are less indicated in ED secondary to neurological
disorders, especially when spinal or local neurogenic path-ways are disrupted. Thus, considering also the common ad-verse effects, their use is restricted to specific clinical conditions.Apomorphine.
Apomorphine is a non selective D1/D2
receptor agonist with moderate efficacy and good tolerability
in the treatment of mild ED . Apomorphine may be in-jected subcutaneously or sublingually assumed; the latter
formulation (2 and 3 mg) has recently been approved for
clinical use in several countries . However, apomorphine
shows lower efficacy and tolerability than sildenafil. Apo-morphine injections have been used for ED in individuals
without PD. As in men with PD apomorphine has been re-ported to cause penile erections and hypersexuality [45, 46],
the drug could be investigated for ED in this neurodegenera-tive disorder.Naltrexone.
Assuming that endogenous opioids may be
involved in sexual dysfunction, it has been shown that
naltrexone, an opiod antagonist, increased the frequency of
morning erection and successful coital attempts [47, 48].Trazodone.
Trazodone is an atypical antidepressant drug,
which selectively inhibits central 5HT uptake and increases
the turnover of brain dopamine. Although its use in the
treatment of ED is still controversial, some pilot studies gave
promising results either in the treatment of individuals with
ED  or with selective serotonin-reuptake inhibitor-induced SD ; furthermore, a combination of trazodone
with sildenafil was effective to restore erectile function of
men with ED and a degree of psychogenic component .Dietary supplements.
Many dietary supplements and
nutriceuticals worldwide used not only have purported bene-fits on erectile function, but also on the cardiovascular sys-tem in general . L-arginine is a NO donor for neural and
endothelial NO-synthase increasing NO production when
consumed in supraphysiologic doses of more than 3 g per
day . To boost NO levels, L-arginine is often combined
with the NO-synthase stimulant pygnogenol, a pine bark
derivative, and this combined approach seems to be effective
even in human ED. Recently, L-arginine was also tested in
combination with adenosine monophosphate in 26 patients
with mild-to-moderate ED ; this pilot phase II study
showed that the on-demand oral administration at a high
dosage of L-arginine aspartate plus adenosine monophos-phate may be effective and well tolerated, although larger
studies are needed.
Although Ginkgo biloba has been used more frequently
to improve cerebrovascular microcirculation, its central ef-fect have been postulated to ameliorate iatrogenic ED. Cohen
AJ invented a method for treating such SD administering an
effective amount of Ginkgo extract (120 to 240 mg/ daily)
Among different varieties of Ginseng which are fre-quently found in dietary supplements, Korean Ginseng has
been most extensively studied in relation to ED, with contro-versial results. However, a recent multicenter, randomized,
double-blind, placebo-controlled study evaluating the effi-cacy of standardized
Korean ginseng berry extract (SKGB)
in 119 men with ED showed significant improvements on
erectile function, ejaculation and other aspects of sexual
function . Finally, an improvement of erectile function
has been described with L-carnitine [57, 58], which acts
through a prostaglandin-induced vasorelaxation of arterioles,
and with a combination of Propionyl-L-carnitine, L-arginine
and niacin , although larger studies are needed.
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