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Activation of dopamine D-4 receptors by ABT-724 induces penile erection in rats
Abbott Laboratories.
Abbott Laboratories.
Abbott Laboratories.
Abbott Laboratories.
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2004 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, no 17, 6758-6763 p.Article in journal (Refereed) Published
Abstract [en]

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 D(4) receptor agonist that activates human dopamine D(4) receptors with an EC(50) 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.

Place, publisher, year, edition, pages
National Academy of Sciences; 1999 , 2004. Vol. 101, no 17, 6758-6763 p.
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Medical and Health Sciences
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URN: urn:nbn:se:liu:diva-59778DOI: 10.1073/pnas.0308292101ISI: 221107900077PubMedID: 15087502OAI: oai:DiVA.org:liu-59778DiVA: diva2:353372
Available from: 2010-09-26 Created: 2010-09-24 Last updated: 2017-12-12

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Hedlund, Petter

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