Calcium Sensitizing and Phosphodiesterase-III Inhibitory Activity of Pyridazine Compounds: A Review

Abstract

Congestive heart disease is one of the main causes of death in the globe, affecting more than 1% of the world population. Various remedial agents are used for the treatment of cardiac diseases such as inotropics and vasodilators. Sympathomimetic drugs play an important role, but they unfortunately undergo severely from oral ineffectiveness and tachyphylaxis due to receptor desensitization. Recently, several cardiac phasphodiestrase-III (PDE-III) inhibitors have been developed with improved ventricular performance and exercise tolerances. Theoretically, PDE-inhibitors combine positive inotropy and vasodilation (known as zinodilator) action and these exceptional features make them very attractive. Various pyridazine drugs act as selective PDE-III inhibitor and characterized by a positive inotropic effect combined with vasodilatory effects. The pyridazine is an important heterocyclic structure with various biologically active compounds with diverse pharmacological activities. Pyridazine hold considerable interest relative to the physiologically active cardiac compounds such as Ca⁺² sensitizing and PDE-III inhibitor activity. However, some pyridazine compounds have been reported as effective agents in the treatment of several cardiovascular diseases including, acute and chronic heart failure, myocardial infarction, angina, arrhythmia, and hypertension. Pyridazinone nucleus has focus attention because of new pyridazinone compounds will design and development of novel Ca⁺² sensitizing and PDE-III inhibitors as cardio tonic agents in future.