Reduced disease in aged rats treated chronically with ibopamine, a catecholaminergic drug.
As part of preclinical safety testing for carcinogenicity, postpubertal (50 days old) rats were dosed (0, 30, 90 or 180 mg/kg/day) with ibopamine (N-methyldopamine, 0,0'-diisobutyroyl ester.HCl; SK&F 100168) for 730 consecutive days. Neoplastic and nonneoplastic lesions were identified histologically in all rats that died during the period of dosing, as well as in those that were killed after it was completed. Six neoplastic lesions (adrenal cortical, mammary, and pituitary adenoma, skin papilloma, pheochromocytoma and mammary adenocarcinoma) and five nonneoplastic lesions (chronic glomerulonephropathy, renal pelvic mineralization, hepatocellular proliferative nodule, galactoceles and chronic cardiomyopathy) were significantly reduced in a dose-related fashion in at least one sex of ibopamine-treated rats. In addition, age-related alopecia and atrophy of the adrenal zona glomerulosa were retarded by ibopamine treatment. Squamous cell skin carcinoma was the only lesion that was significantly (p less than 0.05) increased in the treated groups. Mortality during the study was not significantly different in treated and control groups, indicating that the lower incidence of disease in ibopamine-treated rats was a drug effect and not an artifact of differential survival. Although life span was not measured, ibopamine-treated rats had significantly less malignant lesions than controls at the end of dosing, suggesting a potentially positive effect of treatment on population survival. As the result of these beneficial effects, ibopamine may be useful for future study of factors affecting the occurrence of disease during aging.
Walker
R F
RF
Department of Reproductive and Developmental Toxicology, Smith Kline and French Laboratories, Philadelphia, PA 19101.
Weideman
C A
CA
Wheeldon
E B
EB
D000375:Aging; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003846:Deoxyepinephrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives*; D004435:Eating / Q000187:drug effects; D005260:Female; D008297:Male; D009017:Morbidity; D009374:Neoplasms, Experimental / Q000517:prevention & control; D051381:Rats; D012737:Sex Factors
C023487:ibopamine; D003846:Deoxyepinephrine; D004298:Dopamine