Synthesis and Vasorelaxant Effect of 9-aryl-1,8-acridinediones as Potassium Channel Openers in Isolated Rat Aorta

Authors

  • Asieh Firoozeh-Moghadam Pharmacy Faculty, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Atefeh Shirinbak Pharmacy Faculty, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Farzin Hadizadeh Pharmacy Faculty, Mashhad University of Medical Sciences, Mashhad, Iran. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Mahmoud Seifi Pharmacy Faculty, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Mohammad Bagher Gharedaghi Pharmacy Faculty, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:

ATP-sensitive potassium (KATP) channel openers have a relaxation effect due to the lower cellular membrane potential and inhibit calcium influx. There has been considerable interest in exploring KATP channel openers in the treatment of various diseases such as cardiovascular, cerebrovascular, and urinary system disease and premature labor. The purpose of this study was to synthesize 3,3,6,6-tetramethy l-9-aryl-octahydro-1,8-acridindiones and investigate their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rings of rat aortic smooth muscle. In this study, four new derivatives of 3,3,6,6-tetramethy l-9-aryl-octahydro-1,8-acridindione [2a-d] were synthesized by the reaction of 5, 5-dimethyl-1,3-cyclohexanedione with an aromatic aldehyde, 2-alkylthio-1-(4-fluorobenzyl)-5-formylimidazole or 3-substituted benzaldehyde, in the presence of ammonia in methanol. Their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rat aorta were investigated. Minoxidil was used as a standard potassium channel opener and Glibenclamide was used as a standard potassium channel blocker. The effects of compounds on KCl-induced contractile response which is an indicator of ca-channel blocking activity was also investigated and compared to that of nifedipine as a standard calcium channel blocker. Compounds 3a-d and Minoxidil relaxed the contractions exerted by using phenylephrine with the potency order as follows: Minoxidil > 3c > 3d > 3a > 3b. This effect was sensitive to the potassium channel blocker Glibenclamide. It can be concluded that these compounds act via ATP-sensitive potassium (KATP) channels. Selectivity index (SI) for these compounds and Minoxidil also shows that these compounds are selective to ATP-sensitive potassium (KATP) channels and the selectivity of compounds 3a-d is less than Minoxidil.

Upgrade to premium to download articles

Sign up to access the full text

Already have an account?login

similar resources

Synthesis and Vasorelaxant Effect of 9-aryl-1,8-acridinediones asPotassium Channel Openers in Isolated Rat Aorta

ATP-sensitive potassium (KATP) channel openers have a relaxation effect due to the lower cellular membrane potential and inhibit calcium influx. There has been considerable interest in exploring KATP channel openers in the treatment of various diseases such as cardiovascular, cerebrovascular, and urinary system disease and premature labor. The purpose of this study was to synthesize 3,3,6,6-tet...

full text

synthesis and vasorelaxant effect of 9-aryl-1,8-acridinediones as potassium channel openers in isolated rat aorta

atp-sensitive potassium (katp) channel openers have a relaxation effect due to the lower cellular membrane potential and inhibit calcium influx. there has been considerable interest in exploring katp channel openers in the treatment of various diseases such as cardiovascular, cerebrovascular, and urinary system disease and premature labor. the purpose of this study was to synthesize 3,3,6,6-tet...

full text

Synthesis and Effects of Novel Dihydropyridines as Dual Calcium Channel Blocker and Angiotensin Antagonist on Isolated Rat Aorta

Objective(s) Four novel losartan analogues 5a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of 5a and 5b on angiotensin receptors (AT') and L-type calcium channels were investigated on isolated rat aorta. Materials and Methods Aortic rings were pre-contracted with 1 pM Angiotensin II or 80 mM KCl and relaxant effects of losartan, nifedipine, 5a and...

full text

Vasorelaxant effects of the potassium channel opener SR 47063 on the isolated human saphenous vein and rat aorta.

The vasorelaxant effects of SR 47063 (4-(2-cyanimino-1, 2-dihydropyrid-1-yl)-2,2-dimethyl-6-nitr ochromene), a new K(+)-channel opener structurally related to levcromakalim, were examined in isolated human saphenous vein (HSV) and rat aorta (RA). HSV or RA rings were precontracted with either KCl or noradrenaline and cumulative relaxant concentration-response curves were obtained for SR 47063 (...

full text

Actions of potassium channel openers in rat detrusor urinae.

This study was performed to investigate the action of potassium channel openers on the mechanical activity of detrusor muscle isolated from rats. Detrusor muscle strips, 15 mm in length, were myographied isometrically in an isolated organ bath. P 1060, RP 49356 and BRL 38277, potassium channel activators, reduced the basal tone and diminished the phasic activity of detrusor concentration-depend...

full text

My Resources

Save resource for easier access later

Save to my library Already added to my library

{@ msg_add @}


Journal title

volume 11  issue 1

pages  229- 233

publication date 2011-11-26

By following a journal you will be notified via email when a new issue of this journal is published.

Hosted on Doprax cloud platform doprax.com

copyright © 2015-2023