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 CaCl 2 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.

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

Giovanna Lucıa Delogu
Penultimo
;
2019-01-01

Abstract

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 CaCl 2 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.
calcium channel blockers; endothelium; phthalazinone derivatives; rat aortic rings; synthesis; vasorelaxant activity
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/261906
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