title: Avanafil, a highly selective phosphodiesterase type 5 inhibitor for erectile dysfunction, shows good safety profiles for retinal function and hemodynamics in anesthetized dogs.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Pharmacology Research Laboratories II, Mitsubishi Tanabe Pharma Corp., Saitama, Japan.
authors: Hideki
authors: H
authors: Mochida
authors: Koji
authors: K
authors: Yano
authors: Hirotaka
authors: H
authors: Inoue
authors: Shiyin
authors: S
authors: Yee
authors: Tsunehisa
authors: T
authors: Noto
authors: Kohei
authors: K
authors: Kikkawa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D004596:Electroretinography; D007172:Erectile Dysfunction / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects*; D015398:Signal Transduction; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D011743:Pyrimidines; D013450:Sulfones; D000068677:Sildenafil Citrate; C553414:avanafil
keywords: ERG; MAP; NO; NTG; PAP; PDE; TPR; VRCCA; VRVA; avanafil; cGMP; common carotid artery vascular resistance; cyclic guanosine-3′, 5′ monophosphate; electroretinogram; erectile dysfunction; hypotension; mean arterial pressure; nitric oxide; nitroglycerin; penis; phosphodiesterase; pulmonary arterial pressure; retina; total peripheral resistance; vertebral artery vascular resistance