Pharmacological profile of SL 59.1227, a novel inhibitor of the sodium/hydrogen exchanger

@article{Lorrain2000PharmacologicalPO,
  title={Pharmacological profile of SL 59.1227, a novel inhibitor of the sodium/hydrogen exchanger},
  author={Janine Lorrain and Veronique Briand and E Favennec and Nicole Duval and Alain Grosset and Philip Janiak and Christian Hoornaert and G Cremer and Christopher John Latham and S. E. O'connor},
  journal={British Journal of Pharmacology},
  year={2000},
  volume={131}
}
The NHE1 isoform of the Na+/H+ exchanger plays an important role in the regulation of intracellular pH and in cardiac cell injury caused by ischaemia and reperfusion. SL 59.1227 is a novel imidazolypiperidine Na+/H+ antiport inhibitor which is structurally unrelated to previously described acylguanidine inhibitors such as cariporide. Recovery of pHi following an intracellular acid load was measured in CCL39‐derived PS120 variant cells, selectively expressing either NHE1 or NHE2 isoforms of the… 
An overview of inhibitors of Na(+)/H(+) exchanger.
TLDR
Extensive pre-clinical studies indicated that NHE inhibitors afford substantial protection in different animal models of myocardial ischemia (MI) and reperfusion, but the results of clinical trials involving eniporide and cariporides were mixed.
Inhibitors of sodium-hydrogen exchange as therapeutic agents for the treatment of heart disease
TLDR
Protection of the ischaemic and reperfused myocardium such as during coronary artery surgery, as well as limiting myocardial remodelling and heart failure, will emerge as the two primary targets for NHE-1 inhibitors in cardiovascular therapeutics.
The Cardioprotective Effects of Novel Na+/H+ Exchanger Inhibitor TY-51924 on Ischemia/Reperfusion Injury
Abstract: The inhibitory effects of sodium 3-guanidinocarbonyl-2-methyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-9-ylmethyl sulfate monoethanolate (TY-51924) are selective for Na+/H+ exchanger
Zoniporide: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1).
TLDR
In both in vitro and in vivo rabbit models of myocardial ischemia-reperfusion injury, zoniporide markedly reduced infarct size without adversely affecting hemodynamics or cardiac function.
Is timing everything? Therapeutic potential of modulators of cardiac Na+ transporters
TLDR
The Na+-HCO3- cotransporter (NBC) is also stimulated by intracellular acidification, and part of the benefit of angiotensin-converting enzyme inhibitors after myocardial infarction may be due to inhibition of the NBC.
Antiarrhythmic effects of Na‐H exchange inhibition
The sodium–hydrogen exchange (NHE), which extrudes protons for concomitant sodium influx, represents the primary mechanism by which the cardiac cell regulates its pH, particularly under excessive
Potent and selective inhibition of the human Na+/H+ exchanger isoform NHE1 by a novel aminoguanidine derivative T-162559.
TLDR
It is demonstrated that the acylguanidine derivatives, cariporide and eniporides, cause selective inhibition of hNHE1 and found that a novel synthetic aminoguanidine derivative, T-162559, causes a selective inhibiting of hnHE1 with more potent activity than cariparide andEniporid (IC50 value of 0.96 nM).
NHE-1 inhibition: from protection during acute ischaemia/reperfusion to prevention/reversal of myocardial remodelling
  • W. Linz, A. Busch
  • Medicine
    Naunyn-Schmiedeberg's Archives of Pharmacology
  • 2003
TLDR
NHE-1 inhibitors offer substantial promise for clinical development for attenuation of both a) acute responses to myocardial injury, b) chronic post-infarct and hypertension- and age-related responses resulting in the development of heart failure.
In vitro and in vivo pharmacology of a structurally novel Na+‐H+ exchange inhibitor, T‐162559
TLDR
The results indicate that the new structural NHE‐1 inhibitor T‐162559 is more potent than cariporide and eniporides and possesses a cardioprotective effect against ischaemia and reperfusion injury in rat and rabbit models.
Chemistry of NHE Inhibitors
For more than a decade after the discovery of the Na+/H+ exchanger (NHE) in 1976, amiloride-type agents were the only tools available for the investigation of the consequences of NHE inhibition in
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