Journal of Andrology
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Published-Ahead-of-Print May 25, 2006, DOI:10.2164/jandrol.106.000547

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Doxazosin and Serotonin (5-HT) Receptor (1A, 2A and 4) Antagonists Inhibit 5-HT-Mediated Human Cavernosal Contraction

David H.W. Lau , Cecil S. Thompson , James F Bellringer , Philip J Thomas , Faiz H Mumtaz , Robert J Morgan , and Dimitri P Mikhailidis *

* To whom correspondence should be addressed. E-mail: mikhailidis{at}aol.com.

Penile erection results from the balance between relaxation and contractile mechanisms of the corpus cavernosum. Only few studies suggest a role for endogenous contractile agents such as 5-hydroxytryptamine (5-HT). Our aim was to confirm the possible role of 5-HT on human erection. The effect of 5-HT on human cavernosal tissues as well as those of doxazosin (shown previously to have 5-HT inhibitory action), ketanserin (5-HT(2A) receptor antagonist) , NAN-190 (5-HT(1A) receptor antagonist) and SB 203186 (5-HT(4) receptor antagonist) on 5-HT-mediated effects were assessed using the organ bath technique including electrical field stimulation study (EFS). Results are presented as median (mg/mg=mg contraction/mg of tissue). Consistent 5-HT-mediated (10-3 M) contractions were demonstrated (n=18; 63 mg/mg). These contractions were inhibited with ketanserin by 90% (n=8), NAN-190 by 68% (n=12) and SB 203186 by 55% (n=12). Doxazosin showed a similar 5-HT inhibitory action in a concentration-dependent manner (10-4 M; 94% reduction; n=8, 10-6 M; 68.3% reduction; n=8). Our EFS studies indicated the presence of neuronally derived 5-HT and that a majority of the non-adrenergic contraction (54%) was mediated via 5-HT(2A) receptors. These findings suggest that 5-HT may play a role in the human detumescence process via 5-HT(1A), 5-HT(2A) and 5-HT(4) receptors. Neuronally released 5-HT is probably an important contractile neurotransmitter in the erectile process. Doxazosin, ketanserin and 5-HT(1A) and 5-HT(4) receptor antagonists may be useful as part of combination therapy used to treat erectile dysfunction.


Key words: Erectile Dysfunction • 5-hydroxytryptamine • cavernosal tone • corpus cavernosum




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Home page
 American Journal of Men's HealthHome page
D. H. W. Lau, C. S. Thompson, and D. P. Mikhailidis
The Peripheral Serotonergic Pathway: A New Target for Treating Erectile Dysfunction?
American Journal of Men's Health, March 1, 2008; 2(1): 37 - 39.
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