Cardiodepressant Activity of Newer Dihydropyrimidine Derivative in Comparison to Nifedipine on Perfused Rabbits Heart

Background: Substituted dihydropyridine calcium channel blockers are used in the treatment of cardiovascular diseases. Dihydropyridines are considered as analogue of dihydropyrimidines.Objectives: In present study newly synthesized test compound 5- Acyl-6-methyl-4(2',3'-methylenedioxy) phenyl - 2 - S - ethyl - 1, 4- dihydropyrimidine, a dihydropyrimidine derivative was investigated with an aim to get valuable substitute for the well known dihydropyridine, Nifedipine.Material & Methods: The Calcium Channel blocking actiuity of test compound was studied on Rabbit's Heart and its effects were compared with Nifedipine used as control.Results: Test compound has dose-dependent negative chronotropic and negative inotropic effect on Rabbit's heart but these effects appeared at doses higher than those of Nifedipine. Test compound had no significant change in coronary flow however Nifedipine show significant increase in coronary flow at lower doses.Conclusion: Test compound appears to be less potent myocardial depressant compared to Nifedipine. Test compound produced calcium channel blocking activity which was dose related and in order to ascertain the status of this compound as a drug, further studies are needed not only in other animals and tissue models but also in various pathophysiological models.

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Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers

Turkish Journal of Biochemistry ◽

10.1515/tjb-2016-0247 ◽

2017 ◽

Vol 43 (6) ◽

pp. 578-586 ◽

Cited By ~ 2

Author(s):

Erdem Kamil Ozer ◽

Miyase Gozde Gunduz ◽

Ahmed El-Khouly ◽

Yildirim Sara ◽

Rahime Simsek ◽

...

Keyword(s):

Smooth Muscle ◽

Calcium Channel ◽

Phenyl Ring ◽

Rat Aorta ◽

Channel Blockers ◽

One Pot ◽

H Nmr ◽

Channel Blocking ◽

Blocking Activity ◽

Isolated Rat

AbstractObjectiveThe aim of this study was to synthesize ten 1,4-dihydropyridine (DHP) derivatives in which substituted cyclohexane rings were fused to the DHP ring and to determine how different ester groups and the benzoyl substituent introduced in 4-phenyl ring affected their calcium channel blocking activity.MethodsA microwave-assisted one-pot method was applied for the synthesis of compound1–5according to a modified Hantzsch reaction. The benzoyl moiety was introduced in the 4-phenyl ring of these dihydropyridines by refluxing with benzoyl chloride in acetone in the presence of anhydrous potassium carbonate. Synthesized products were characterized by elemental analysis, IR,1H-NMR and13C-NMR spectroscopy. The inhibitory actions of compounds1–10on calcium channel blocking activity were tested on isolated rat aorta preparations.ResultsThe obtained pharmacological results showed that although all compounds are potent relaxing agents on isolated rat aorta smooth muscle, introduction of a benzoyloxy substitiuent on the phenyl ring (compound6–10) decreased the relaxant effect of these compunds.ConclusionThe reported 1,4-DHP derivatives have calcium channel blocking activity on rat aorta smooth muscle.

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Voltage Gated Sodium Channel Blockers: Synthesis of Mexiletine Analogues and Homologues

Current Medicinal Chemistry ◽

10.2174/0929867327666200504080530 ◽

2020 ◽

Vol 27 ◽

Author(s):

Alessia Catalano ◽

Carlo Franchini ◽

Alessia Carocci

Keyword(s):

Sodium Channel ◽

Channel Blocker ◽

Parent Compound ◽

Channel Blockers ◽

Sodium Channel Blocker ◽

Starting Point ◽

Channel Blocking ◽

Blocking Activity ◽

Synthetic Routes ◽

Lateral Sclerosis

: Mexiletine is an antiarrhythmic drug belonging to IB class, acting as sodium channel blocker. Besides its well-known activity on arrhythmias, its usefulness in the treatment of myotonia, myotonic distrophy and amyotrophic lateral sclerosis is now widely recognized. Nevertheless, it has been retired from the market in several countries because of its undesired effects. Thus, several papers were reported in the last years about analogues and homologues of mexiletine being endowed with a wider therapeutic ratio and a more selectivity of action. Some of them showed sodium channel blocking activity higher than the parent compound. It is noteworthy that mexiletine is used in therapy as a racemate even though a difference in the activities of the two enantiomers were widely demonstrated, with (–)-(R)-enantiomer being more active: this finding led several research groups to study mexiletine and its analogues and homologues in their optically active forms. This review summarizes the different synthetic routes used to obtain these compounds. They could represent an interesting starting point to new mexiletine-like compounds without common side effects related to the use of mexiletine.

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Synthesis and Evaluation of a New Class of Nifedipine Analogs with T-Type Calcium Channel Blocking Activity

Molecular Pharmacology ◽

10.1124/mol.61.3.649 ◽

2002 ◽

Vol 61 (3) ◽

pp. 649-658 ◽

Cited By ~ 56

Author(s):

P. Phani Kumar ◽

Stephanie C. Stotz ◽

R. Paramashivappa ◽

Aaron M. Beedle ◽

Gerald W. Zamponi ◽

...

Keyword(s):

Calcium Channel ◽

New Class ◽

Channel Blocking ◽

Blocking Activity

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The Management of Preterm Labor with the Calcium Channel-Blocking Agent Nifedipine Combined with the β-Mimetic Terbutaline

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808501900507 ◽

1985 ◽

Vol 19 (5) ◽

pp. 369-371 ◽

Cited By ~ 16

Author(s):

Alan F. Kaul ◽

Rapin Osathanondh ◽

Leonard E. Safon ◽

Fredric D. Frigoletto ◽

Paul A. Friedman

Keyword(s):

Calcium Channel ◽

Calcium Channel Blockers ◽

Preterm Labor ◽

Case Reports ◽

Blocking Agent ◽

Channel Blockers ◽

Channel Blocking

We describe a successful, prolonged, inhibition of preterm labor using nifedipine combined with terbutaline in a patient undergoing complicated obstetrical problems. Delivery was delayed for two months and no significant ill effects were observed in the mother or her infant. This case reports the longest duration and the safe use of nifedipine for tocolysis, to date. A review of reports of the use of calcium channel-blockers in preterm labor is also presented.

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