Discovery of new phthalazinones as vasodilator agents and novel pharmacological tools to study calcium channels.

Aim: Hydralazine has led to the synthesis of phthalazinone derivatives which induce vasorelaxation.

Methods

A new series of 2-(aminoalkyl)-4-benzyl-2H-phthalazin-1-one derivatives has been synthesized to study their vasorelaxant activity.

Results

At the highest-studied concentration, most of the new compounds relaxed the denuded aortic rings precontracted with phenylephrine by 72.9-85.7%. Compound 25 (C25) suppressed almost totally the contractile effects of phenylephrine, high KCl concentration, ionomycin and caffeine related to the activation of Ca2+ channels, whereas its inhibitory effect was reversed with high CaCl2 concentrations.

Conclusion

Vasodilator effects of C25 appear to be due exclusively to the reversible blockage of different calcium channels. As broad range calcium channel blocker, C25 seems to be suitable as a pharmacological tool for calcium channel research.