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 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.
Financial & competing interests disclosure
This work was supported by Consellería de Cultura, Educación e Ordenación Universitaria (10PXIB203303PR and Centro Singular de Investigación de Galicia acreditación 2016–2019, ED431G/05) and the European Regional Development Fund (ERDF). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed
No writing assistance was utilized in the production of this manuscript.
Ethical conduct
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.