Bronchodilator and Positive Inotropic Activity of Pyridazine Compound Zardaverine as a Phosphodiesterase Isozymes Inhibitor
DOI:
https://doi.org/10.12970/2308-8044.2015.03.01.4Keywords:
Pyridazinone, phosphodiesterase, zardaverine, bronchodilatorAbstract
The zardaverine is a pyridazinone derivative that has been initiated as an effective broncho-dilatory agent. It is also uses as a positive inotropic agent. The effect of zardaverine is due to the inhibition of phasphodiestrase (PDE) activity. The zardaverine acts on the different PDE isozymes and showed selective PDE-III and PDE-IV isozymes inhibitory activity. The zardaverine reduced the cyclic GMP-controllable PDE III isoenzyme and the rolipram- controllable PDE-IV isoenzyme from canine trachea and human polymorphonuclear (PMN) cells. The zardaverine influenced the calmodulin-motivated PDE-I isoenzyme, the cGMP-motivated PDE-II isoenzyme and the cGMP-specific PDE-V isoenzyme slightly at level up to 100 µM. The zardaverine inhibited the ADP-induced human platelets aggregation. This reduction was synergistically increasing by the adenylate cyclase activators like prostaglandin E1 (PGE1) and forskolin. The zardaverine was reduced the zymosan-induced superoxide anion formation in human PMN cells. This activity was raised by adenylate cyclase activators.
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