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Activation of dopamine D-4 receptors by ABT-724 induces penile erection in rats

Brioni, JD; Moreland, RB; Cowart, M; Hsieh, GC; Stewart, AO; Hedlund, Petter LU ; Donnelly-Roberts, DL; Nakane, M; Lynch, JJ and Kolasa, T, et al. (2004) In Proceedings of the National Academy of Sciences 101(17). p.6758-6763
Abstract
Apomorphine, a nonselective dopamine receptor agonist, facilitates penile erection and is effective in patients suffering from erectile dysfunction. The specific dopamine receptor subtype(s) responsible for its erectogenic effect is not known. Here we report that the dopamine D-4 receptor plays a role in the regulation of penile function. ABT-724 is a selective dopamine D4 receptor agonist that activates human dopamine D-4 receptors with an EC50 of 12.4 nM and 61% efficacy, with no effect on dopamine D-1, D-2, D-3, or D-5 receptors. ABT-724 dose-dependently facilitates penile erection when given s.c. to conscious rats, an effect that is blocked by haloperidol and clozapine but not by domperidone. A proerectile effect is observed after... (More)
Apomorphine, a nonselective dopamine receptor agonist, facilitates penile erection and is effective in patients suffering from erectile dysfunction. The specific dopamine receptor subtype(s) responsible for its erectogenic effect is not known. Here we report that the dopamine D-4 receptor plays a role in the regulation of penile function. ABT-724 is a selective dopamine D4 receptor agonist that activates human dopamine D-4 receptors with an EC50 of 12.4 nM and 61% efficacy, with no effect on dopamine D-1, D-2, D-3, or D-5 receptors. ABT-724 dose-dependently facilitates penile erection when given s.c. to conscious rats, an effect that is blocked by haloperidol and clozapine but not by domperidone. A proerectile effect is observed after intracerebroventricular but not intrathecal administration, suggesting a supraspinal site of action. s.c. injections of ABT-724 increase intracavernosal pressure in awake freely moving rats. In the presence of sildenafil, a potentiation of the proerectile effect of ABT-724 is observed in conscious rats. The ability of ABT-724 to facilitate penile erection together with the favorable side-effect profile indicates that ABT-724 could be useful for the treatment of erectile dysfunction. (Less)
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Proceedings of the National Academy of Sciences
volume
101
issue
17
pages
6758 - 6763
publisher
National Acad Sciences
external identifiers
  • pmid:15087502
  • wos:000221107900077
  • scopus:2342509138
ISSN
1091-6490
DOI
10.1073/pnas.0308292101
language
English
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6dc9c832-eaea-4968-a259-138cde0f5fe0 (old id 280109)
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2007-08-02 11:05:19
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@article{6dc9c832-eaea-4968-a259-138cde0f5fe0,
  abstract     = {Apomorphine, a nonselective dopamine receptor agonist, facilitates penile erection and is effective in patients suffering from erectile dysfunction. The specific dopamine receptor subtype(s) responsible for its erectogenic effect is not known. Here we report that the dopamine D-4 receptor plays a role in the regulation of penile function. ABT-724 is a selective dopamine D4 receptor agonist that activates human dopamine D-4 receptors with an EC50 of 12.4 nM and 61% efficacy, with no effect on dopamine D-1, D-2, D-3, or D-5 receptors. ABT-724 dose-dependently facilitates penile erection when given s.c. to conscious rats, an effect that is blocked by haloperidol and clozapine but not by domperidone. A proerectile effect is observed after intracerebroventricular but not intrathecal administration, suggesting a supraspinal site of action. s.c. injections of ABT-724 increase intracavernosal pressure in awake freely moving rats. In the presence of sildenafil, a potentiation of the proerectile effect of ABT-724 is observed in conscious rats. The ability of ABT-724 to facilitate penile erection together with the favorable side-effect profile indicates that ABT-724 could be useful for the treatment of erectile dysfunction.},
  author       = {Brioni, JD and Moreland, RB and Cowart, M and Hsieh, GC and Stewart, AO and Hedlund, Petter and Donnelly-Roberts, DL and Nakane, M and Lynch, JJ and Kolasa, T and Polakowski, JS and Osinski, MA and Marsh, K and Andersson, Karl-Erik and Sullivan, JP},
  issn         = {1091-6490},
  language     = {eng},
  number       = {17},
  pages        = {6758--6763},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Activation of dopamine D-4 receptors by ABT-724 induces penile erection in rats},
  url          = {http://dx.doi.org/10.1073/pnas.0308292101},
  volume       = {101},
  year         = {2004},
}