Combination of alfuzosin and tadalafil exerts in vitro an additive relaxant effect on human corpus cavernosum.
BACKGROUND
Phosphodiesterase type 5 (PDE5) inhibitors, such as tadalafil, are a first-line treatment for erectile dysfunction (ED). Nevertheless, some patients do not respond to this treatment. Clinical data suggest that the addition of alpha1-adrenoceptor blocker, such as alfuzosin, commonly prescribed for lower urinary tract symptoms suggestive of benign prostatic hyperplasia, may be of benefit. Aim. Evaluation of the effect of alfuzosin, tadalafil or the combination of both on human corpus cavernosum.


METHODS
Human cavernosal tissues were obtained from 10 patients undergoing penile surgery. Strips contractility was studied in organ baths. Concentration-response curves to tadalafil were generated on norepinephrine (NE, 1-10 microM)-precontracted strips in the presence of alfuzosin or vehicle. Frequency-response curves (FRC) to electrical field stimulation (EFS, 0-64 Hz, 3 ms, 10 seconds, 300 mA) were generated in the presence of vehicle, alfuzosin, tadalafil, or both drugs combined. EFS (20 Hz, 1 ms, 10 seconds, 300 mM)-induced nitrergic relaxation on NE-precontracted strips was studied in the presence of vehicle, alfuzosin, tadalafil, or both drugs combined.


METHODS
Functional measurement of cavernosal smooth muscle relaxation in the presence of tadalafil and alfuzosin.


RESULTS
The relaxation induced by tadalafil (10(-10) to 10(-5) M) on precontracted strips was enhanced by alfuzosin at both 10(-8) and 10(-7) M. The combination of alfuzosin (3.10(-8) M) and tadalafil (10(-7) M) was more efficient to inhibit FRC-induced contractions than each compound alone. The combination of tadalafil (10(-6) M) and alfuzosin (10(-8) M) increased the relaxation induced by EFS and its effect was greater than tadalafil alone. In addition, the combination of tadalafil (10(-6) M) and alfuzosin (10(-7) M) prolonged EFS-induced relaxation to a greater extent than each compound alone.


CONCLUSIONS
In vitro, the combination of alfuzosin and tadalafil is more efficient than each compound alone to relax adrenergic tone or to enhance nitrergic relaxation of the human corpus cavernosum. Such a combination deserves further investigation in placebo-controlled studies to evaluate its benefit in ED patients who are not sufficiently improved by PDE5 inhibitors.
Oger
Stephanie
S
Pelvipharm, Paris, France.
Behr-Roussel
Delphine
D
Pelvipharm, Paris, France.
Gorny
Diane
D
Pelvipharm, Paris, France.
Charles Tremeaux
Jack
J
Clinique Sainte Marthe, Dijon, France.
Combes
Michel
M
Clinique Pasteur, Royan, France.
Alexandre
Laurent
L
Pelvipharm, Paris, France.
Giuliano
François
F
Raymond Poincaré Hospital-Department of Physical Medicine and Rehabilitation, Garches, France. Electronic address: giuliano@cyber-sante.org.
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D002243:Carbolines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D000068581:Tadalafil
D000317:Adrenergic alpha-Antagonists; D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D011799:Quinazolines; D009569:Nitric Oxide; D000068581:Tadalafil; C047638:alfuzosin