Pumafentrine is benzonaphthyridine derivative patented by BYk Gulden Lomberg Chemische Fabrik G.m.b.H. as phosphodiesterase (PDE) inhibitor useful for bronchial treatment. In preclinical trials, Pumafentrine acts as a mixed selective PDE-3/4 inhibitor. Treatment with pumafentrine from week 4 to 6 after a single injection of monocrotaline (partially reversed pulmonary hypertension and right heart hypertrophy in rats. In addition, small pulmonary arterial muscularization, medial hypertrophy and decrease in lumen area were largely reversed. Inhibition of smooth muscle proliferation under pumafentrine was demonstrated in vivo as was a pro-apoptotic effect of pumafentrine on vascular cells. Moreover, pumafentrine dose-dependently increased cyclic adenosine monophosphate levels and inhibited proliferation of cultured pulmonary arterial smooth muscle cells. Pumafentrine was used in phase 2 clinical trials for the treatment of asthma but was discontinued in 2002, reportedly due to a short duration of action. An active metabolite of pumafentrine, hydroxypumafentrine, has also been described, although there have been no published clinical data on this compound