Discolouration of the Optic Disc in Baboons During Treatment with Prizidilol (SK&F 92657), a Novel Antihypertensive Agent

Abstract

1 Prizidilol (SK&F 92657-A2.H2O) is the dihydrochloride salt of D,L-3-[2-(3- t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine, a molecule combining the properties of precapillary vasodilatation and β-adrenoceptor blockade. 2 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. 3 Discolouration of the optic disc did not appear to affect visual function. 4 Slow regression of discolouration was demonstrated after withdrawal of treatment with 800 mg of prizidilol/kg at 6 months. 5 No histological abnormalities were present in the optic discs of affected baboons. 6 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.