Pharmacotherapy for erectile dysfunction.
BACKGROUND
Advances in understanding of the biochemistry and physiology of penile erection have led to breakthroughs in pharmacotherapy of erectile dysfunction.


OBJECTIVE
To provide recommendations/guidelines concerning state-of-the-art knowledge for the putative molecular and cellular mechanisms of action of centrally and peripherally acting drugs currently utilized in pharmacotherapy of erectile dysfunction.


METHODS
An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a two-year period. Concerning the Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10 countries.


METHODS
Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate.


RESULTS
Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, induces and increases penile erection responses via disinhibition, following sexual stimulation.


CONCLUSIONS
There is a need for more research in the pharmacotherapeutic development of central and peripheral agents for safe and effective erectile dysfunction treatment.
Padma-Nathan
Harin
H
hpn@insyght.com
Christ
George
G
Adaikan
Ganesan
G
Becher
Edgardo
E
Brock
Gerald
G
Carrier
Serge
S
Carson
Culley
C
Corbin
Jackie
J
Francis
Sharon
S
DeBusk
Robert
R
Eardley
Ian
I
Hedlund
Hans
H
Hutter
Adolph
A
Jackson
Graham
G
Kloner
Robert
R
Lin
Ching-Shwun
CS
Lin
Shin
S
McVary
Kevin
K
McCullough
Andrew
A
Nehra
Ajay
A
Porst
Hartmut
H
Schulman
Claude
C
Seftel
Allen
A
Sharlip
Ira
I
Stief
Christian
C
Teloken
Claude
C
D001058:Apomorphine / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D007546:Isoquinolines; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000627:therapeutic use; D009287:Naphthyridines / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D012725:Sexual Behavior / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D014196:Trazodone / Q000627:therapeutic use; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000627:therapeutic use
D001058:Apomorphine; D018491:Dopamine Agonists; D007546:Isoquinolines; D009271:Naltrexone; D009287:Naphthyridines; D018696:Neuroprotective Agents; D010456:Peptides, Cyclic; D010726:Phosphodiesterase Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors; D014196:Trazodone; D000521:alpha-MSH; C079282:melanotan-II; C060956:Delequamine; C038981:nalmefene