Discolouration of the optic disc in baboons during treatment with prizidilol (SK&F 92657), a novel antihypertensive agent.
Prizidilol (SK&F 92657-A2 X H2O) is the dihydrochloride salt of D,L-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazi ne, a molecule combining the properties of precapillary vasodilatation and beta-adrenoceptor blockade. Prizidilol was administered to baboons daily for up to 1 year at sustained doses up to 800 mg/kg. During the 16th week of a 26-week study ophthalmoscopic examination revealed an orange tinge at the periphery of the normally pale pink optic disc in all high-dose (800-1225 mg/kg) baboons. The colour became more intense as the study progressed. By week 25 orange discolouration was seen in all baboons at 350 mg/kg and three out of six baboons at 100 mg/kg. The findings, except those at 100 mg/kg, were confirmed in a 12-month study. Optic disc discolouration was correlated with darkening of internal organs at necropsy. Discolouration of the optic disc did not appear to affect visual function. Slow regression of discolouration was demonstrated after withdrawal of treatment with 800 mg of prizidilol/kg at 6 months. No histological abnormalities were present in the optic discs of affected baboons. The study demonstrates the value of regular ophthalmoscopy in toxicity studies, combining the facility for the early detection of an unusual lesion with the ability to follow its time-course.
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D009898:Optic Disk / Q000187:drug effects* / Q000473:pathology; D010215:Papio; D010859:Pigmentation Disorders / Q000139:chemically induced*; D011724:Pyridazines / Q000633:toxicity*; D012025:Reflex, Pupillary / Q000187:drug effects; D013997:Time Factors; D014792:Visual Acuity / Q000187:drug effects
D000959:Antihypertensive Agents; D011724:Pyridazines; C024293:prizidilol