Neutral endopeptidase inhibition: could it have a role in the treatment of female sexual arousal disorder?
Female sexual arousal disorder (FSAD) is the inability to attain or maintain an adequate lubrication-swelling response of sexual excitement. The potentiation of vascular responses leading to increased blood flow in clitoris and vagina has represented the main focus in the pharmacological treatment of FSAD, including the evaluation of the type 5 phosphodiesterase (PDE5) inhibitors. However, due to a lack of clear efficacy, there is no approved pharmacotherapy for FSAD to date. In the present issue of the British Journal of Pharmacology, Wayman et al. show that the administration by intravenous or intravaginal routes of a novel neutral endopeptidase inhibitor, UK-414,445, results in enhanced genital blood flow responses to pelvic nerve stimulation in female rabbits, without significantly affecting blood pressure. Neutral endopeptidase inhibition, by preserving vasoactive peptides such as vasoactive intestinal polypeptide, raises the possibility of a new pharmacological approach to the treatment of FSAD.
Angulo
Javier
J
Departamento de Investigación, Hospital Universitario Ramón y Cajal, Madrid, Spain. javier.angulo@hrc.es
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D005836:Genitalia, Female / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000502:physiology*; D010388:Pelvis / Q000294:innervation; D010421:Pentanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012726:Sexual Behavior, Animal / Q000187:drug effects; D020018:Sexual Dysfunctions, Psychological / Q000188:drug therapy* / Q000503:physiopathology; D013830:Thiadiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014660:Vasoactive Intestinal Peptide / Q000502:physiology
D010421:Pentanoic Acids; D013830:Thiadiazoles; C550955:UK-414,495; D014660:Vasoactive Intestinal Peptide; D015260:Neprilysin
Nat Rev Urol. 2009 Apr;6(4):216-22
19352396
J Sex Med. 2010 Feb;7(2 Pt 1):758-68
19912487
Int J Impot Res. 1995 Jun;7(2):91-100
7496446
J Sex Med. 2009 Mar;6 Suppl 3:286-91
19267851
Int J STD AIDS. 2007 Feb;18(2):130-1
17331290
J Sex Med. 2009 Jun;6(6):1561-1568
19453923
J Anat. 1996 Jun;188 ( Pt 3):633-44
8763480
Diabetes. 1990 May;39(5):608-12
2185111
Int J Impot Res. 2003 Apr;15(2):137-41
12789394
Diabetes Care. 2009 May;32(5):780-5
19407075
Diab Vasc Dis Res. 2009 Jan;6(1):38-9
19156627
J Sex Med. 2010 Jan;7(1 Pt 2):586-614
20092454
Peptides. 1987 Sep-Oct;8(5):797-800
3432128
Br J Pharmacol. 2010 May;160(1):51-9
20412068