105102-18-9

phosphodiesterase

The effect of the phosphodiesterase inhibitor Tibenelast, and placebo on isoproterenol-induced changes in heart rate, cAMP and norepinephrine levels in normal male volunteers is studied. Tibenelast increases the heart rate response to isoproterenol infusion, whereas norepinephrine and cAMP levels are not different in any treatment.

Tibenelast is a potent orally active compound against anaphylactic shock induced by high dose antigen aerosol. When a lower aerosol challenge (0.05 mg/mL) is employed, bronchoconstriction is observed with a concomitant increase in lung resistance (RL) and a fall in dynamic compliance (Cdyn). Tibenelast at 25 mg/kg p.o. prevents these changes. Tibenelast is 10 times more potent than Aminophylline by i.v. administration; normalization of pulmonary function is achieved at 1 mg/kg i.v. Tibenelast is synergistic with epinephrine. The oral dose response curve of Tibenelast is enhanced with the co-administration of epinephrine. Tibenelast may be of significant value in the treatment of asthma and other respiratory diseases.