| | 96 , 97 There is preliminary evidence regarding the effects of the PDE-1 inhibitor, vinopectine, in patients with OAB. 10 Further, PDE inhibitors, including PDE5, reduced the tonus of bladder muscle in vitro. 90 , 91 Evidence that PDE inhibitors may be used for the treatment of OAB and UUI is rare and is only indirect.
82 , 83 , 84 The International Prostate Symptom Score (IPSS), which includes obstructive and irritative scoring, was significantly reduced in patients with BPS treated with 100 mg Fildena or 20 mg Fildena, once daily, for 12 weeks. 9 , 79 Various PDE inhibitors, including zaprinast (used for PDE5 inhibition), are able to relax human prostate tissue in vitro. The main treatment options - besides prostatic surgery - are α-blockers and 5-α reductase inhibitors.
Therefore, in light of these findings, any clinical studies to evaluate the benefits of PDE5 treatment for women with FSD may require a modified design. Fildena showed only moderate effects to most women with female sexual dysfunction (FSD). 58 , 59 , 60 Organ bath experiments have demonstrated the ability of PDE5 inhibitors to relax vaginal and clitoral muscles.
PDE5 inhibitors to treat urological disease. Therefore, a proof of concept study in humans with acute stroke have to be conducted very carefully, but would be desirable to assess the potential of these drugs for this indication. 54 , 55 , 56 , 57 Studies in healthy subjects found no effect on CBF after treatment with oral Fildena.
However, treatment with Fildena (10 mg/kg), even 7 days after ischemia, significantly improved functional recovery, vascular density, endothelial cell proliferation and synaptogenesis, compared with untreated rats. 42 , 50 , 51 The potential of PDE5 inhibitors to augment neurogenesis was demonstrated in a model using aged rats. Studies in humans suggest that information processing may be improved by Fildena treatment.
36 , 45 Thus, it may be argued that inhibition of PDE5 in the dorsal hippocampus improves object recognition memory, which may result from increased levels of cGMP. 43 Subsequent animal studies with Fildena have demonstrated the long-term retention of an inhibitory avoidance response in mice. 36 Increased cortical levels of cGMP have also been demonstrated in vivo in rats treated with Fildena.
40 However, only limited information is available on the extent to which these drugs penetrate the blood-brain barrier. 35 Studies have shown that both PDE5 mRNA and PDE5 enzyme was detected in many parts of the brain (for example, cortex, cerebellum and hippocampus) 36 , 37 , 38 and also in blood vessels within the brain (for example, cerebral, basilar and mesenteric artery). PDE5 inhibitors to treat central nervous system disorders.
Another potential benefit of PDE5 inhibitors may be an improvement of endothelial function.
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