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Avanafil, a Highly Selective Phosphodiesterase Type 5 Inhibitor for Erectile Dysfunction, Shows Good Safety Profiles for Retinal Function and Hemodynamics in Anesthetized Dogs

2013; Lippincott Williams & Wilkins; Volume: 190; Issue: 2 Linguagem: Inglês

10.1016/j.juro.2013.01.017

1527-3792

Hideki Mochida, Koji Yano, Hirotaka Inoue, Shiyin Yee, Tsunehisa Noto, Kohei Kikkawa,

Migraine and Headache Studies

No AccessJournal of UrologyInvestigative Urology1 Aug 2013Avanafil, a Highly Selective Phosphodiesterase Type 5 Inhibitor for Erectile Dysfunction, Shows Good Safety Profiles for Retinal Function and Hemodynamics in Anesthetized Dogs Hideki Mochida, Koji Yano, Hirotaka Inoue, Shiyin Yee, Tsunehisa Noto, and Kohei Kikkawa Hideki MochidaHideki Mochida Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author , Koji YanoKoji Yano Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author , Hirotaka InoueHirotaka Inoue Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author , Shiyin YeeShiyin Yee Financial interest and/or other relationship with Vivus. More articles by this author , Tsunehisa NotoTsunehisa Noto Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author , and Kohei KikkawaKohei Kikkawa Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.01.017AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We evaluated the effects of the highly selective phosphodiesterase type 5 inhibitor avanafil on electroretinogram and hemodynamics in dogs, and compared the effects with those of sildenafil. Materials and Methods: Three experiments were performed in anesthetized dogs, including determination of the 1) influence on electroretinogram induced by a light adapted 30 Hz flicker stimulation, 2) direct hemodynamic changes and 3) potentiation of nitroglycerin induced hypotension. Avanafil was administered at doses that were pharmacologically equipotent to or higher than those of sildenafil for penile tumescence. Results: 1) Intraduodenal doses of avanafil did not influence the electroretinogram waveform. In contrast, sildenafil changed the waveform shape and significantly delayed time to the peak of the electroretinogram positive waveform (vs vehicle p <0.05). 2) Intravenous infusion of avanafil or sildenafil (1 to 300 μg/kg per minute) significantly decreased systemic blood pressure, total peripheral resistance and pulmonary arterial pressure (vs vehicle p <0.05). Administration of sildenafil but not avanafil significantly decreased the resistance of common carotid and vertebral arteries (vs vehicle p <0.05). 3) Intraduodenal doses of avanafil or sildenafil (0.1 and 1 mg/kg) potentiated the AUC of nitroglycerin induced hypotension. However, the potentiating effect of avanafil at 1 mg/kg was significantly weaker than that of sildenafil (p <0.05). Conclusions: Data suggest that avanafil has a favorable safety profile for erectile dysfunction, which is attributable to its high inhibitory selectivity for phosphodiesterase type 5 against type 6 (retina) and 1 (vessels, etc), respectively, and its short acting pharmacodynamic property. References 1 : Physiological role of cGMP and cGMP-dependent protein kinase in the cardiovascular system. Rev Physiol Biochem Pharmacol1989; 113: 41. Google Scholar 2 : New insights into cGMP action. Adv Second Messenger Phosphoprotein Res1990; 24: 411. Google Scholar 3 : Intracellular cyclic GMP receptor proteins. FASEB J1993; 7: 328. Google Scholar 4 : Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ Res2003; 93: 280. Google Scholar 5 : Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol Rev2011; 91: 651. Google Scholar 6 : Expression, distribution and regulation of phosphodiesterase 5. Curr Pharm Des2006; 12: 3439. 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(SY), Mountain View, California© 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 190Issue 2August 2013Page: 799-806 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordserectile dysfunctionhypotensionpenisavanafilretinaAcknowledgmentsAvanafil and sildenafil were synthesized at Mitsubishi Tanabe Pharma Corp., Osaka, Japan.MetricsAuthor Information Hideki Mochida Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author Koji Yano Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author Hirotaka Inoue Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author Shiyin Yee Financial interest and/or other relationship with Vivus. More articles by this author Tsunehisa Noto Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author Kohei Kikkawa Financial interest and/or other relationship with Mitsubishi Tanabe Pharma. More articles by this author Expand All Advertisement PDF downloadLoading ...