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© 1992 Oxford University Press

research-article

Preclinical Safety Evaluation of Dilevalol (SCH 19927), an Antihypertensive Agent, in the Rat

FRED SELAN1, C. BRUCE MCCULLOUGH and HUGH E. BLACK

Safety Evaluation Center, Schering-Plough Corporation Lafayette, New Jersey 07848

Received June 24, 1991; accepted October 9, 1991

Dilevalol (SCH 19927) is an antihypertensive agent with direct vasodilating properties due to ß2-adrenergic receptor agonist activity and nonselective ß-receptor blocking activity. In acute (single dose) oral and parenteral studies a low order of toxicity was observed. Clinical signs observed at the higher doses included salivation, prostration, tremors, and convulsions. In multidose oral studies dilevalol produced an increase in mean absolute and/or relative heart weights observed as early as 1 month in the high-dose (300 mg/kg) rats and at all dose levels (35, 90, 220 mg/kg) in rats treated for 1 year. There were no microscopic changes that could be associated with the change in heart weight. Intraalveolar macrophages were observed in the lung tissue of rats treated for 3 months or 1 year with an increase in relative lung weights noted in the high-dose (220 mg/kg) group treated for 1 year. In a 2-year rat study, no evidence of oncogenicity was observed. On the basis of these studies, dilevalol has a low order of toxicity and lacks oncogenic potential in the rat.


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