PURPOSE: We investigated the in vitro inhibitory effects of avanafil, a novel, 
potent inhibitor of phosphodiesterase-5, on 11 phosphodiesterases. We also 
studied its potentiation of penile tumescence in dogs.
MATERIALS AND METHODS: Phosphodiesterase assay was done with the 4 
phosphodiesterase-5 inhibitors avanafil, sildenafil, vardenafil and tadalafil 
using 11 phosphodiesterase isozymes. In anesthetized dogs the pelvic nerve was 
repeatedly stimulated to evoke tumescence. Intracavernous pressure was measured 
after avanafil or sildenafil administration.
RESULTS: Avanafil specifically inhibited phosphodiesterase-5 activity at a 50% 
inhibitory concentration of 5.2 nM. Avanafil showed higher selectivity 
(121-fold) against phosphodiesterase-6 than sildenafil and vardenafil (16 to 
21-fold) and showed excellent selectivity (greater than 10,000-fold) against 
phosphodiesterase-1 compared with sildenafil (375-fold). Avanafil also had 
higher selectivity against phosphodiesterase-11 than tadalafil (greater than 
19,000 vs 25-fold). Avanafil also showed excellent selectivity against all other 
phosphodiesterases. After intravenous administration in anesthetized dogs the 
200% effective dose of avanafil and sildenafil on the penile tumescence was 37.5 
and 34.6 μg/kg, respectively. After intraduodenal administration the 200% 
effective dose of avanafil and sildenafil on tumescence was 151.7 and 79.0 μg/kg 
at the peak time, respectively. Time to peak response with avanafil and 
sildenafil was 10 and 30 minutes, respectively, indicating a more rapid onset of 
avanafil.
CONCLUSIONS: Avanafil has a favorable phosphodiesterase-5 selectivity profile 
compared to that of marketed phosphodiesterase-5 inhibitors. Avanafil shows 
excellent in vitro and in vivo potency, and fast onset of action for penile 
erection. Cumulative data suggest that avanafil has a promising pharmacological 
profile for erectile dysfunction.