title: Sildenafil-induced reversible impairment of rod and cone phototransduction in monkeys.
abstract: OBJECTIVE
  To investigate functional alteration of the retina induced by sildenafil in monkeys.
  
  
  METHODS
  Sildenafil was administered intravenously to cynomolgus monkeys at dose levels of 0, 1, 3, and 10 mg/kg, and standard full-field electroretinograms (ERGs) were recorded. The rod and cone a-waves in response to high-intensity flashes were also analyzed by the a-wave fitting model (a-wave analysis). Additionally, the photopic negative responses were recorded.
  
  
  RESULTS
  Sildenafil at 3 mg/kg or more induced the following alterations in the standard full-field ERGs immediately after dosing: delayed b-wave in the rod response; delayed a-wave in the combined rod-cone response; and attenuated b-waves in the single-flash cone response and in the 30 Hz flicker. Additionally, the following changes were observed in the 10 mg/kg group: attenuated b-wave in the rod response; attenuated a-wave and delayed b-wave in the combined rod-cone response; delayed oscillatory potentials; and attenuated and delayed a-wave in the single-flash cone response. In the a-wave analysis immediately after dosing, sildenafil selectively decreased the sensitivity parameter (S) in the cone a-wave at 3 mg/kg, and in both the rod and cone a-waves at 10 mg/kg. The S value was highly correlated with plasma sildenafil concentration. The above changes fully recovered 24 hours after dosing.
  
  
  CONCLUSIONS
  Sildenafil produced reversible impairment of the rod and cone phototransduction in monkeys. Meanwhile, involvement of the postreceptoral retinal components was suggested. These findings contribute to the clarification of sildenafil-induced visual disturbances. It is suggested that the photoreceptors are predominantly, but not exclusively, affected in the retina of humans with sildenafil-induced visual disturbances.
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Kinoshita
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Shimoda
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Kimotsuki
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D004596:Electroretinography / Q000187:drug effects; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D009887:Ophthalmoscopy; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects*; D010879:Piperazines / Q000009:adverse effects* / Q000493:pharmacokinetics; D011687:Purines / Q000009:adverse effects / Q000493:pharmacokinetics; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000009:adverse effects* / Q000493:pharmacokinetics; D014786:Vision Disorders / Q000139:chemically induced* / Q000503:physiopathology; D014785:Vision, Ocular / Q000187:drug effects*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D000068677:Sildenafil Citrate
keywords: drug-induced visual disturbance; electroretinogram; monkey; phototransduction; sildenafil