Sildenafil, N-desmethyl-sildenafil and Zaprinast enhance photoreceptor response in the isolated rat retina.
Here we report that the active component of Viagra, Sildenafil and the first metabolite, N-desmethyl-sildenafil (UK-103, 320) increased the amplitude of flash-evoked electroretinogram (ERG) of dark-adapted albino rat retina. Effects of Sildenafil and N-desmethyl-sildenafil were comparable to those of the known phosphodiesterase inhibitor, Zaprinast. The photoreceptor cell response was isolated by blocking the glial K(+) ion-buffering and the on-bipolar components of the ERG with the use of BaCl(2) (500 microM) and the specific type VI metabotropic glutamate receptor agonist, DL-2-amino-4-phosphonobutyric acid (25 microM), respectively. Zaprinast, Sildenafil and N-desmethyl-sildenafil (1 microM each) increased the amplitude of photoreceptor cell response either. Besides, Sildenafil was significantly more effective than N-desmethyl-sildenafil. These findings suggest an increased sensitivity of photoreceptor cells in the presence of Sildenafil and it is metabolite.
Barabás
Péter
P
Department of Neurochemistry, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeri út 59-67, H 1025, Budapest, Hungary.
Riedl
Zsuzsanna
Z
Kardos
Julianna
J
D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D011688:Purinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000502:physiology*; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011688:Purinones; D013450:Sulfones; D000068677:Sildenafil Citrate; C011145:zaprinast