Ocular changes induced in the beagle dog by intravenous infusion of a novel dopaminergic compound, FPL 65447.
FPL 65447, a selective D1 receptor agonist with a potential for the acute treatment of renal and cardiac failure and of sepsis and septic shock, was administered to beagle dogs by continuous intravenous infusion for a maximum of 14 days. Ophthalmoscopical examination revealed dose-related changes in the eye and associated structures, consisting of foci of retinal discolouration, corneal changes including oedema, keratitis, opacities and neovascularisation, and inflammation of the iris, periorbital tissues, and adnexa. Microscopical examination confirmed the presence of inflammatory lesions in the eye. These were predominantly histiocytic and were mainly focal circumscribed lesions. More diffuse inflammation with a granulocytic and lymphocytic component was also encountered in the limbus and uveal tract. A predominantly interstitial histiocytic adenitis involving various glandular structures associated with the eye and adnexa was also identified. Possible mechanisms to account for the histiocytic changes are discussed.
Kerry
P J
PJ
Fisons plc, Pharmaceutical Division, R&D Laboratories, Leicestershire, United Kingdom.
Wakefield
I D
ID
Evans
J G
JG
D000818:Animals; D003231:Conjunctivitis / Q000139:chemically induced / Q000473:pathology; D003316:Corneal Diseases / Q000139:chemically induced / Q000473:pathology; D004285:Dogs; D004298:Dopamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D015259:Dopamine Agents / Q000008:administration & dosage / Q000633:toxicity*; D005128:Eye Diseases / Q000139:chemically induced* / Q000473:pathology; D007262:Infusions, Intravenous; D008199:Lymphadenitis / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009887:Ophthalmoscopy; D017447:Receptors, Dopamine D1 / Q000187:drug effects
D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; C084449:FPL 65447; D004298:Dopamine