Why the study?
Does long-term administration of the phosphodiesterase inhibitor ICI 153,110 cause glandular and mucosal alterations in rats?
Does long-term administration of the phosphodiesterase inhibitor ICI 153,110 cause glandular and mucosal alterations in rats?
Long-term administration of the phosphodiesterase inhibitor ICI 153,110 in rats causes significant glandular and mucosal alterations, likely due to altered cyclic nucleotide metabolism.
May inform safety monitoring in PDE inhibitor development; leaves open human relevance.
The inotropic vasodilator, ICI 153,110, a phosphodiesterase inhibitor intended for the treatment of congestive heart failure, was administered to Alderley Park Wistar-derived rats for periods of up to 182 days. Treatment produced hypertrophy of salivary glands, hyperplasia of intestinal mucosa, and dacryoadenitis of the harderian gland. As the functions of these glandular tissues can be modified by factors which alter cyclic nucleotide metabolism, it is postulated that the glandular alterations produced by ICI 153,110 occurred as a result of phosphodiesterase inhibition.
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Westwood et al. (1991) studied this question.
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