In search of the digitalis replacement

Abstract

There are now several new CT drugs undergoing clinical study for the treatment of CHF. While most of these new agents are like digitalis in that they possess significant inotropic activity, they differ from digitalis in that they tend to also have pronounced vasodilator properties. Such compounds, because they are not pure CT agents, should not be regarded as true digitalis replacements. Despite the increased understanding about the cAMP cascade and about cardiac muscle contraction in general, the long search for a specific digitalis replacement cannot be regarded as having been accomplished. It should also be noted that the initial clinical assessment for any of these new compounds will be complicated by the fact that they are tested in only the latter stages of CHF where prognosis is very poor and the possibility of showing significant improvement in mortality is extremely difficult. It will be unfortunate if the potential for positive inotropic agents (pure CT drugs) is compromised by clinical studies that employ mixed inotropic-vasodilator compounds in extremely sick patient populations. The continued use of the digitalis glycosides for such a long period of history implies that at least some subpopulation of CHF patients should derive benefit from therapy with an appropriately selective CT drug. Neither the appropriate drug nor the appropriate specific patient population, both of which are needed to properly address the eventual role of inotropic therapy in CHF, have, as yet, been identified.

Green and High Efficient Synthesis of 2-Aryl Benzimidazoles: Reaction of Arylidene Malononitrile and 1,2-Phenylenediamine Derivatives in Water or Solvent-Free Conditions

“…These compounds exhibit activity against several viruses include HIV [7] [8], influenza [9], herpes (HSV-1) [10], RNA [11] and human cytomegalovirus (HCMV) [12]. They have also been employed as antihypertensive, antiviral, anticancer, antiulcer, antifungal and untihistamine [13]- [18].…”

Microwave Assisted Synthesis of Benzimidazoles Catalysed by Oxalic Acid

“…They are also inhibitors of photosynthesis, aldose reductase and antagonist of neurotransmitter receptors. They also are found to exhibit appreciable herbicidal activity (2)(3)(4). The most prominent benzimidazole compound in nature is N-ribosyl-dimethylbenzimidazole, which serves as an axial ligand for cobalt in vitamin B12 (5).…”

Synthesis and calcium channel modulation effects of isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-phenylpyridine-5-carboxylates possessingortho-,meta-, andpara-CH2S(O)nMe and -S(O)nMe (n = 0-2) phenyl substituents

“…Accordingly, the design of cardioselective DHP CC agonists (positive inotropes), that act at the L-type voltage dependent CC, has presented a significant drug design challenge [Langs and Triggle, 1985;Langs et al, 1990Langs et al, , 1991Mager et al, 1992]. In this regard, the prototype 1,4-DHP CC agonist Bay K 8644 (1) [Schramm et al, 1983] simultaneously promotes calcium entry into vascular smooth muscle, causing vasoconstriction, that precludes its clinical use for the treatment of congestive heart failure (CHF) Preuss et al, 1985;Erhardt, 1987].…”