Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats

Jorge D. Brioni, Robert B. Moreland, Marlon Cowart, Gin C. Hsieh, Andrew O. Stewart, Petter Hedlund, Diana L. Donnelly-Roberts, Masaki Nakane, James J. Lynch, Teodozyi Kolasa, James S. Polakowski, Mark A. Osinski, Kennan Marsh, Karl Erik Andersson, James P. Sullivan

Research output: Contribution to journalArticle

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 D4 receptor plays a role in the regulation of penile function. ABT-724 is a selective dopamine D 4 receptor agonist that activates human dopamine D4 receptors with an EC50 of 12.4 nM and 61% efficacy, with no effect on dopamine D1, D2, D3, or D5 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.

Original languageEnglish
Pages (from-to)6758-6763
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number17
DOIs
Publication statusPublished - Apr 27 2004

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats'. Together they form a unique fingerprint.

  • Cite this

    Brioni, J. D., Moreland, R. B., Cowart, M., Hsieh, G. C., Stewart, A. O., Hedlund, P., Donnelly-Roberts, D. L., Nakane, M., Lynch, J. J., Kolasa, T., Polakowski, J. S., Osinski, M. A., Marsh, K., Andersson, K. E., & Sullivan, J. P. (2004). Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats. Proceedings of the National Academy of Sciences of the United States of America, 101(17), 6758-6763. https://doi.org/10.1073/pnas.0308292101