Phosphodiesterase

ICI 153110 is an orally active phosphodiesterase inhibitor with both vasodilating and inotropic properties which is designed for the treatment of congestive cardiac failure. Fourteen animals have died as a direct or indirect consequence of ICI 153110 administration in the high-dose main test and reversibility groups. In the female rat dosed at 10 mg/kg/day ICI 153110 a mild focal arteritis is characterized by a predominantly and diffusely adventitial infiltration of mixed cells and early formation of fibrous tissue. The two rats dosed at 250 mg/kg/day ICI 153110 die prematurely from intratracheal intubation of dosing solution. Arteries from two further animals (dosed at 5 and 250 mg/kg/day ICI 153110) show minimal focal arteritis with medial necrosis, and medial and adventitial inflammation.